Academic literature on the topic 'DIFFERENTIALLY REGULATED GENES'

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Journal articles on the topic "DIFFERENTIALLY REGULATED GENES"

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Rodrigues, Paulo H., and Ann Progulske-Fox. "Gene Expression Profile Analysis of Porphyromonas gingivalis during Invasion of Human Coronary Artery Endothelial Cells." Infection and Immunity 73, no. 9 (September 2005): 6169–73. http://dx.doi.org/10.1128/iai.73.9.6169-6173.2005.

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ABSTRACT Microarrays were used to identify genes of Porphyromonas gingivalis W83 differentially expressed during invasion of primary human coronary artery endothelial cells. Analyses of microarray images indicated that 62 genes were differentially regulated. Of these, 11 genes were up-regulated and 51 were down-regulated. The differential expression of 16 selected genes was confirmed by real-time PCR.
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Jagoueix-Eveillard, Sandrine, Frank Tarendeau, Karine Guolter, Jean-Luc Danet, Joseph M. Bové, and Monique Garnier. "Catharanthus roseus Genes Regulated Differentially by Mollicute Infections." Molecular Plant-Microbe Interactions® 14, no. 2 (February 2001): 225–33. http://dx.doi.org/10.1094/mpmi.2001.14.2.225.

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A differential display of mRNAs was used to isolate periwinkle cDNAs differentially expressed following infection with one of three mollicutes: Spiroplasma citri, Candidatus Phytoplasma aurantifolia, and stolbur phytoplasma. Twenty-four differentially expressed cDNAs were characterized by Northern blots and sequence analysis. Eight of them had homologies with genes in databanks coding for proteins involved in photosynthesis, sugar transport, response to stress, or pathways of phytosterol synthesis. The regulation of these genes in periwinkle plants infected by additional phloem-restricted bacteria showed that they were not specific to a given mollicute, but correlations with particular symptoms could be established. Expression of transketolase was down regulated following infection with a pathogenic strain of S. citri. No down regulation was observed for the nonphytopathogenic mutant GMT553, which is deficient for fructose utilization.
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Jin, Long, Jian Ping Yu, Zai Jun Yang, Juha Merilä, and Wen Bo Liao. "Modulation of Gene Expression in Liver of Hibernating Asiatic Toads (Bufo gargarizans)." International Journal of Molecular Sciences 19, no. 8 (August 10, 2018): 2363. http://dx.doi.org/10.3390/ijms19082363.

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Hibernation is an effective energy conservation strategy that has been widely adopted by animals to cope with unpredictable environmental conditions. The liver, in particular, plays an important role in adaptive metabolic adjustment during hibernation. Mammalian studies have revealed that many genes involved in metabolism are differentially expressed during the hibernation period. However, the differentiation in global gene expression between active and torpid states in amphibians remains largely unknown. We analyzed gene expression in the liver of active and torpid Asiatic toads (Bufo gargarizans) using RNA-sequencing. In addition, we evaluated the differential expression of genes between females and males. A total of 1399 genes were identified as differentially expressed between active and torpid females. Of these, the expressions of 395 genes were significantly elevated in torpid females and involved genes responding to stresses, as well as contractile proteins. The expression of 1004 genes were significantly down-regulated in torpid females, most which were involved in metabolic depression and shifts in the energy utilization. Of the 715 differentially expressed genes between active and torpid males, 337 were up-regulated and 378 down-regulated. A total of 695 genes were differentially expressed between active females and males, of which 655 genes were significantly down-regulated in males. Similarly, 374 differentially expressed genes were identified between torpid females and males, with the expression of 252 genes (mostly contractile proteins) being significantly down-regulated in males. Our findings suggest that expression of many genes in the liver of B. gargarizans are down-regulated during hibernation. Furthermore, there are marked sex differences in the levels of gene expression, with females showing elevated levels of gene expression as compared to males, as well as more marked down-regulation of gene-expression in torpid males than females.
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Wan, Guoqiang, Wenyang Zhou, Yang Hu, Rui Ma, Shuilin Jin, Guiyou Liu, and Qinghua Jiang. "Transcriptional Regulation of lncRNA Genes by Histone Modification in Alzheimer’s Disease." BioMed Research International 2016 (2016): 1–4. http://dx.doi.org/10.1155/2016/3164238.

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Increasing studies have revealed that long noncoding RNAs (lncRNAs) are not transcriptional noise but play important roles in the regulation of a wide range of biological processes, and the dysregulation of lncRNA genes is associated with disease development. Alzheimer’s disease (AD) is a chronic neurodegenerative disease that usually starts slowly and gets worse over time. However, little is known about the roles of lncRNA genes in AD and how the lncRNA genes are transcriptionally regulated. Herein, we analyzed RNA-seq data and ChIP-seq histone modification data from CK-p25 AD model and control mice and identified 72 differentially expressed lncRNA genes, 4,917 differential peaks of H3K4me3, and 1,624 differential peaks of H3K27me3 between AD and control samples, respectively. Furthermore, we found 92 differential peaks of histone modification H3K4me3 are located in the promoter of 39 differentially expressed lncRNA genes and 8 differential peaks of histone modification H3K27me3 are located upstream of 7 differentially expressed lncRNA genes, which suggest that the majority of lncRNA genes may be transcriptionally regulated by histone modification in AD.
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Jefferies, D., M. Botman, C. Farquharson, D. Lester, C. C. Whitehead, B. H. Thorp, and B. Houston. "Cloning differentially regulated genes from chondrocytes using agarose gel differential display." Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression 1396, no. 3 (March 1998): 237–41. http://dx.doi.org/10.1016/s0167-4781(97)00234-0.

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Arvidsson, Gustav, and Anthony Wright. "A Protein Intrinsic Disorder Approach for Characterising Differentially Expressed Genes in Transcriptome Data: Analysis of Cell-Adhesion Regulated Gene Expression in Lymphoma Cells." International Journal of Molecular Sciences 19, no. 10 (October 10, 2018): 3101. http://dx.doi.org/10.3390/ijms19103101.

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Conformational protein properties are coupled to protein functionality and could provide a useful parameter for functional annotation of differentially expressed genes in transcriptome studies. The aim was to determine whether predicted intrinsic protein disorder was differentially associated with proteins encoded by genes that are differentially regulated in lymphoma cells upon interaction with stromal cells, an interaction that occurs in microenvironments, such as lymph nodes that are protective for lymphoma cells during chemotherapy. Intrinsic disorder protein properties were extracted from the Database of Disordered Protein Prediction (D2P2), which contains data from nine intrinsic disorder predictors. Proteins encoded by differentially regulated cell-adhesion regulated genes were enriched in intrinsically disordered regions (IDRs) compared to other genes both with regard to IDR number and length. The enrichment was further ascribed to down-regulated genes. Consistently, a higher proportion of proteins encoded by down-regulated genes contained at least one IDR or were completely disordered. We conclude that down-regulated genes in stromal cell-adherent lymphoma cells encode proteins that are characterized by elevated levels of intrinsically disordered conformation, indicating the importance of down-regulating functional mechanisms associated with intrinsically disordered proteins in these cells. Further, the approach provides a generally applicable and complementary alternative to classification of differentially regulated genes using gene ontology or pathway enrichment analysis.
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Buzzio, Oscar L., Zhenxiao Lu, Curt D. Miller, Terry G. Unterman, and J. Julie Kim. "FOXO1A Differentially Regulates Genes of Decidualization." Endocrinology 147, no. 8 (August 1, 2006): 3870–76. http://dx.doi.org/10.1210/en.2006-0167.

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The forkhead box O1A (FOXO1A) has been identified as one gene that is up-regulated early in the decidualization process. To further investigate the role of FOXO1A during this process, six genes, IGFBP1, PRL, TIMP3, LAMB1, CNR1, and DCN, shown to be up-regulated during decidualization, were chosen as potential targets of FOXO1A action. Treatment of human endometrial stromal cells with hormones (estradiol and medroxyprogesterone acetate) plus dibutyryl cAMP (H+dbcAMP) for 48 h increased expression of IGFBP1, PRL, TIMP3, CNR1, and DCN but not LAMB1, as measured by real-time PCR. Silencing of FOXO1A using small interfering RNA oligonucleotides decreased IGFBP1 and DCN levels and increased CNR1, TIMP3, and PRL levels. LAMB1 was not affected. When FOXO1A was overexpressed in human endometrial stromal cells, expression of IGFBP1, DCN, and PRL increased, whereas levels of TIMP3 and CNR1 decreased. Addition of H+dbcAMP caused an increased expression of IGFBP1, PRL, and DCN beyond that of FOXO1A alone. TIMP3 and CNR1 levels decreased even further in response to H+dbcAMP compared with FOXO1A alone. LAMB1, which was unresponsive to FOXO1A, decreased when H+dbcAMP was added. Overexpressing FOXO1A also caused a change in cell shape, in that the stromal fibroblasts acquired a rounded, epithelioid appearance. Finally, reporter studies showed that cotransfection of FOXO1A significantly increased PRL promoter activity but not TIMP3 promoter activity. Addition of H+dbcAMP resulted in a significant increase in PRL promoter activity and a significant decrease in TIMP3 promoter activity. In summary, this study demonstrates the versatile nature of FOXO1A in the regulation of a number of decidualization-specific genes.
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Dedonder, A., R. Rethy, H. Fredericq, M. Van Montagu, and E. Krebbers. "Arabidopsis rbcS Genes Are Differentially Regulated by Light." Plant Physiology 101, no. 3 (March 1, 1993): 801–8. http://dx.doi.org/10.1104/pp.101.3.801.

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Elalfy, Mahmoud M., and Jürgen Borlak. "Exon Array Analysis to Identify Diethyl-nitrosamine Differentially Regulated and Alternately Spliced Genes in Early Liver Carcinogenesis in the Transgenic Mouse ATT-myc Model." SciMedicine Journal 3, no. 2 (June 1, 2021): 138–52. http://dx.doi.org/10.28991/scimedj-2021-0302-6.

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Objectives: To identify the regulated genes or the spliced genes of diethylnitorsamine (NDEA) in ATT-myc mice versus control group. Methods: We analysed the 9 hybridizations on the MouseExon10ST array of NDEA treatments and control non- transgenic by application of a mixed model analysis of variance. Results: The 907 genes had regulated significantly between the groups and 916 genes had regulated with a significant exon-group interaction among of them 150 genes had regulated with both gene and possible splicing differences (p<0.01). The 7,618 genes had tested for the alternative gene up-regulation and splicing and compared to the gene-classifications. The genes functions, pathways and gene-classifications in the current study had presented in the contingency table analysis of the set of the regulated genes and alternatively spliced that regulated significantly in the ATT-myc mice treated by diethylnitorsamine versus control non-transgenic. The GOMolFn of gene-classification had 321 groups that had significantly regulated in the set of the regulated genes or differentially spliced. While the GOProcess of gene-classification had 330 groups that had significantly regulated in the set of differentially regulated genes or spliced. Additionally, the CELlLoc of gene-classification had 70 groups that had significantly regulated in the set of differentially regulated genes spliced. Finally, the Pathway gene-classification had 8 groups that had significantly regulated in the set of differentially regulated genes or spliced (p<0.01) in diethylnitorsamine when compared to control group. Conclusion: we summarized the toxicogenomics induced by diethylnitrosamine in early liver carcinogenesis in ATT-myc transgenic mice of liver cancer. Doi: 10.28991/SciMedJ-2021-0302-6 Full Text: PDF
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Fuchun, Si, Yue Jingyu, and Si Gao. "Screening of differentially expressed genes of esophageal squamous cell carcinoma with cDNA microarray." Journal of Clinical Oncology 37, no. 15_suppl (May 20, 2019): e13005-e13005. http://dx.doi.org/10.1200/jco.2019.37.15_suppl.e13005.

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e13005 Background: Esophageal Carcinoma (EC) is one of the most common malignant tumors in digestive system and is the sixth leading cause of cancer-related mortality worldwide. To find out the genes related with the occurrence and development of EC can help to elucidate the pathogenesis and molecular mechanism of it. The aim of the present study was to find out differentially expressed genes of EC in different stages(cancerous tissue, paraneoplastic tissue, normal mucosa tissue) by cDNA microarray technique, so that to provide new molecular biomarker and approach for the treatment and diagnosis of EC, and contribute to comprehensively knowing the mechanism of EC occurrence and development. Methods: The whole RNA of 21 cases of EC cancerous tissue, paraneoplastic tissue and normal mucosa tissue were extracted, then using agarose gel electrophoresis to make quality control, Agilent human genome 4*44K gene chip was applied to screen differentially expressed genes. Results: 2659 differential expression genes between cancerous tissue and normal mucosa tissue were screened, included 1328 up-regulated genes and 1331 down-regulated genes; 2505 differential expression genes between cancerous tissue and paraneoplastic tissue were screened, included 1286 up-regulated genes and 1218 down-regulated genes. 48 significant up-regulation genes and 11 significant down-regulation genes were reported in association with EC for the first time. Through GO classification, screened differentially expressed genes mainly were involved in the following function and process: catalytic activity, signal transduction, molecular transport and combination, enzymatic activity regulation, transcription activity regulation, protein transportation function, cell growth and apoptosis, and so on. Conclusions: The screened differential expression genes of EC in different stages may provide experimental basis for further illuminating the occurrence mechanism of esophageal squamous carcinoma.
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Dissertations / Theses on the topic "DIFFERENTIALLY REGULATED GENES"

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Imada, Minatelli Sabrina Yuri [Verfasser], Uwe [Akademischer Betreuer] Groß, Uwe [Gutachter] Groß, Fabian Moritz [Gutachter] Commichau, and Wolfgang [Gutachter] Bohne. "Characterization of genes differentially regulated after bile acid exposure in Campylobacter jejuni / Sabrina Yuri Imada Minatelli ; Gutachter: Uwe Groß, Fabian Moritz Commichau, Wolfgang Bohne ; Betreuer: Uwe Groß." Göttingen : Niedersächsische Staats- und Universitätsbibliothek Göttingen, 2019. http://d-nb.info/1193728371/34.

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Watkinson, Jonathan I. "Characterization of two genes, trehalose-6-phosphate synthase/phosphatase and nucleotide binding protein, shown to be differentially regulated in roots of Cypripedium parviflorum var. pubescens grown with a mycorrhizal fungus Thanatephorus pennatus." Diss., Virginia Tech, 2002. http://hdl.handle.net/10919/27467.

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The analysis of gene changes associated with formation of the mycorrhizal symbiosis between orchid and fungi could have broad implications for plant pathogen interactions. Fungi associated with North American terrestrial orchids were once included in the pathogenic genus Rhizoctonia. This suggests that orchids are able to overcome or utilize normally pathogenic pathways to establish symbioses. A differential display technique was employed to analyze gene changes in orchid in response to a fungus. Samples of RNA from roots of Cypripedium parviflorum var. pubescens (CyPP) grown in the presence or absence of a mycorrhizal fungus; Thanatephorus pennatus, were analyzed using AFLP differential display. Forty-four fragments were selected out of 5000 as being differentially expressed, but only 15 sequences were obtained. Most showed homology to ribosomal genes. Two represented genes believed to be regulated by the mycorrhizal interaction: trehalose-6-phosphate synthase/phosphatase (Tps), which showed down-regulation and nucleotide binding protein (NuBP), which showed up-regulation. The Tps partial clone identifies 2100 bp at the 3' end of the gene and encodes a protein of 667 amino acids. The NuBP gene is approximately 1200bp in length and encodes a protein of 352 amino acids. The Tps gene exists in multiple copies with high expression in roots and low expression in rhizomes and leaves. The NuBP gene exists as a single copy and has a low level of expression in rhizomes and leaves. Expression of Tps is induced by sucrose, but reduced by trehalose. Cultivation of CyPP with non-mycorrhizal fungi did not affect expression of Tps or NuBP. Trehalose induced NuBP expression whereas sucrose did not. A second species of mycorrhizal fungi induced expression of NuBP but reduced expression of Tps. Analysis of Tps expression in Arabidopsis was done using promoter:GUS fusions. The Tps promoter:GUS plants revealed that Tps expression is constitutive in roots. Regulation of Tps driven GUS is expressed throughout seedlings. GUS was not detected in leaves of older plants but was detected in anthers and stigmatic surfaces of flowers. Expression of GUS driven by Tps showed a strong wound response and was present in the junction between siliques and pedicels.
Ph. D.
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Ezer, Nadine. "Gene expression is differentially regulated in the epididymis after orchidectomy." Thesis, McGill University, 2002. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=78357.

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The epididymis is the site for the transport, maturation and storage of spermatozoa. It is well established that epididymal structure and function are dependent on the testis for circulating androgens and factors in luminal fluid. Using cDNA microarrays, our objective is to characterize the expression of genes that are regulated over the first week post-orchidectomy in the epididymis of the adult Brown Norway rat. We describe four patterns of gene expression that are simultaneously activated in the epididymis after orchidectomy. We identify potential androgen-dependent genes including glutathione S-transferases and calcium-binding proteins, as well as potential androgen-repressed genes such as glutathione peroxidase-1. The expression of heat shock proteins, cyclins, and apoptosis-associated genes are described in the epididymis after orchidectomy. These results form the first comprehensive analysis of testis-regulated gene expression in the epididymis. This study is the first to demonstrate that gene expression is differentially regulated in the epididymis after orchidectomy.
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Daniels, Damon. "NF-κB-regulated differential gene transcription : a systems biology analysis." Thesis, University of Manchester, 2015. https://www.research.manchester.ac.uk/portal/en/theses/nfkappabregulated-differential-gene-transcription-a-systems-biology-analysis(f25d85c4-5463-4d41-bbb0-d23e6265fda8).html.

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The NF-κB transcription factor is expressed in the majority of mammalian cells and regulates a large number of genes with important functions in a variety of cellular processes including cell growth, division, apoptosis and inflammatory responses. Perturbation of NF-κB response has been implicated in a variety of diseases such as asthma and inflammatory bowel disease, in addition to various forms of cancer. Through experiments at the single cell level it has been shown that NF-κB displays complex temporal activation, notably including nucleo-cytoplasmic oscillations. It has been observed that these oscillations occur in a heterogeneous manner; as such they are masked when measured at the population level. In contrast, pulsed TNFα treatment at 100 min intervals produces regular and synchronous nuclear peaks of NF-κB. Such pulsatile stimulation may reflect more accurately physiological conditions. The work in this project uses a Systems Biology approach consisting of bioinformatic, mathematical, and experimental methodologies to investigate how NF-κB can regulate such a diverse set of gene responses. Previously published studies have proposed that target gene expression levels following NF-κB activation (continuous TNFα) can be explained by a combination of key parameters, including transcript degradation rate, transcript structure, and transcription initiation rate. Initial work in this project highlighted that these explanatory factors are not sufficient to describe the observed temporal order of gene transcription. The roles of miRNAs and NF-κB subunit phosphorylation in regulation were additionally explored. A large set of genes was identified that are activated more strongly by pulsed TNFα than by continuous TNFα treatment. This suggests a new unreported mechanism of gene regulation, the possible causes of which are examined in this thesis. The gene list was refined by altering pulse frequency, which revealed an enrichment of NF-κB targets correlated with the regularity of these pulses. Temperature shift and anti-inflammatory drug treatment (Diclofenac) were shown to have a profound effect on NF-κB oscillation frequency. These perturbations provide an alternative method to study the effects of NF-κB oscillation frequency on specific target genes, independent of a pulse regime. Integration and analysis of these datasets suggested that a core, frequency-encoded set of genes regulated by NF-κB might exist. It is proposed that such genes may respond optimally to specific frequencies of NF-κB activation, implying a potential frequency threshold. The presence of such genes may explain the need for the complex systems that control NF-κB timing. It was noted that there was an enrichment of genes encoding transcription factors within the frequency encoding set, in addition to proteins which are known to be involved in the control of inflammation.
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Styczynska-Soczka, Katarzyna. "Regulation and function of Rootletin, a gene differentially expressed in Drosophila sensory neurons." Thesis, University of Edinburgh, 2015. http://hdl.handle.net/1842/15889.

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Drosophila melanogaster is a widely used and efficient genetic model to study nervous system development. The conservation of many genes from Drosophila to vertebrates and a short reproduction cycle makes the fruitfly a great tool for providing insight into crucial events in nervous system formation. In studying the development of the sensory nervous system, Drosophila also provides a model for understanding the formation and function of structurally diverse cilia. Cilia are hairlike organelles present throughout our bodies and responsible for many processes such as chemo, mechano, and thermosensation, fluid movement, hearing and fertility. In Drosophila the only somatic ciliated cells are the Type I sensory neurons in which a cilium forms the sensory dendrite. There are more than two diverse subtypes of the ciliated sensory neurons and the mechanism by which this diversity is achieved remains unclear. The mechanism of ciliated sensory neuron differentiation was hereby studied on an example of a differentially expressed ciliary gene - CG6129 - a Drosophila orthologue of human Rootletin, a main protein components of ciliary rootlets. CG6129 expression is specific to the ciliated cells and exhibits so called chordotonal-enriched pattern - a strong and permanent expression in the chordotonal subtype of type I neurons and weaker and transient expression in the external sensory subtype. I have shown that CG6129 knock-down causes severe disruption of the chordotonal organs function without any obvious change in the structure of the cilium, other than the lack of ciliary rootlet. The function of the external sensory subtype was only slightly affected which further highlights the difference between the two types of ciliated sensory organs. The fact that CG6129 is differentially expressed in the two subtypes of the Drosophila ciliated sensory neurons suggests that the genes involved in the formation of various cilia are differentially regulated. I have shown that CG6129 is regulated by the two well known ciliary transcription factors - RFX and fd3F (distant homologue of Foxj1). Of the two enhancers found the early-to-late enhancer is almost entirely dependent on RFX and not on fd3F while the late enhancer is dependent on both fd3F and RFX. The fact that there is some residual CG6129 expression in the absence of both RFX and fd3F suggests involvement of another regulator that may contribute to the cilia diversity. Zmynd10 is a recently characterised ciliary gene that is involved in the axonemal dynein arms assembly. Mutations in human Zmynd10 cause primary ciliary dyskinesia (PCD) and Drosophila Zmynd10 mutants have immotile cilia that lack dynein arms. Due to the presence of specific protein domains Zmynd10 has been suggested to act as a transcriptional regulator. I have shown that the transcript levels of CG6129 and other ciliary genes are reduced in the Zmynd10 mutant. This implies that Zmynd10 may regulate ciliary genes on a transcriptional or post transcriptional level and may contribute to the regulatory network governing ciliogenesis.
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Tsourdi, Elena, Juliane Salbach-Hirsch, Martina Rauner, Tilman D. Rachner, Stephanie Möller, Matthias Schnabelrauch, Dieter Scharnweber, and Lorenz C. Hofbauer. "Glycosaminoglycans and their sulfate derivatives differentially regulate the viability and gene expression of osteocyte-like cell lines." Sage, 2014. https://tud.qucosa.de/id/qucosa%3A35689.

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Collagen and glycosaminoglycans, such as hyaluronan and chondroitin sulfate, are the major components of bone extracellular matrix, and extracellular matrix composites are being evaluated for a wide range of clinical applications. The molecular and cellular effects of native and sulfatemodified glycosaminoglycans on osteocytes were investigated as critical regulators of bone remodeling. The effects of glycosaminoglycans on viability, necrosis, apoptosis, and regulation of gene expression were tested in two osteocyte-like cell lines, the murine MLO-Y4 and the rat UMR 106-01 cells. Glycosaminoglycans were non-toxic and incorporated by osteocytic cells. In MLO-Y4 cells, sulfation of glycosaminoglycans led to a significant inhibition of osteocyte apoptosis, 42% inhibition for highly sulfated chondroitin sulfate and 58% for highly sulfated hyaluronan, respectively. Cell proliferation was not affected. While treatment with highly sulfated chondroitin sulfate increased cell viability by 20% compared to the native chondroitin sulfate. In UMR 106- 01 cells, treatment with highly sulfated hyaluronan reduced the receptor activator of nuclear factor-κB ligand/osteoprotegerin ratio by 58% compared to the non-sulfated form, whereas highly sulfated chondroitin sulfate led to 60% reduction in the receptor activator of nuclear factor-κB ligand/osteoprotegerin ratio in comparison to the native chondroitin sulfate. The expression of SOST, the gene encoding sclerostin, was reduced by 50% and 45% by highly sulfated hyaluronan and chondroitin sulfate, respectively, compared to their native forms. The expression of BMP- 2, a marker of osteoblast differentiation, was doubled after treatment with the highly sulfated hyaluronan in comparison to its native form. In conclusion, highly sulfated glycosaminoglycans inhibit osteocyte apoptosis in vitro and promote an osteoblast-supporting gene expression profile.
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Williamson, William Iain. "Differential chromatin topology and transcription factor enhancer binding regulate spatiotemporal gene expression in limb development." Thesis, University of Edinburgh, 2013. http://hdl.handle.net/1842/8056.

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Many developmental genes are located in gene-poor genomic regions and are activated by long-range enhancers located up to 1Mb away. Modification and reorganisation of chromatin structure is pivotal to such long-range gene regulation. A prerequisite for enhancer activity is the binding of transcription factors and co-factors with the interplay between activating and repressive factors determining tissue, spatial and temporal specificity. Spatiotemporal control of sonic hedgehog (Shh) and the 5′ Hoxd genes (especially Hoxd13) is crucial for vertebrate limb anterior-posterior (A-P) axis and autopod patterning. Shh tissue specificity is controlled by multiple enhancers throughout an adjacent gene desert. The ~0.8Mb-distant limb enhancer (ZRS) bypasses nearby genes to activate only Shh. In contrast, limb-specific HoxD expression is regulated by multiple enhancers, with the ~200kb-distant global control region (GCR) regulatory element the most characterised. In this thesis I investigated the mechanisms of ZRS and GCR regulation of Shh and Hoxd13 respectively. The model system used was immortalised cell lines derived from the anterior and posterior distal forelimb buds of E10.5 and E11.5 mouse embryos. Cell line data were confirmed in dissected limb tissue. Increased expression of the 5′ Hoxd genes, particularly Hoxd13, correlated with the loss of the repressive, polycomb catalysed, histone modification H3K27me3 and decompaction of chromatin structure over the HoxD locus at the distal posterior forelimb bud at stage E10.5. Moreover, I show that the GCR spatially co-localises with the 5′ HoxD locus at the distal posterior region of E10.5-11 embryos. These data are consistent with the formation of a chromatin loop between Hoxd13 and the GCR at the time and place of distal limb bud development when the GCR is required to initiate 5′ Hoxd gene expression. This is the first example of A-P differences in chromatin compaction and local folding in the limb. Point mutations within the ZRS cause ectopic (anterior) Shh expression, which results in preaxial polydactyly (PPD). The ZRS contains multiple canonical ETS transcription factor binding motifs, and point mutations in two families with PPD results in the formation of additional ETS binding sites. The point mutations cause the loss or reduction of ETV4/5 transcription factor binding at a non-canonical ETS binding site and enable additional binding instead of ETS1. I show that ETV4/5, ETS1 and another ETS protein GABPα all bind to the ZRS. This work has revealed the differential effect on Shh expression of two groups of ETS factors mediated through the ZRS. The binding of ETS1/ GABPα determines the posterior Shh expression domain while ETV4/5 restricts anterior Shh expression. Two point mutations alter the ETS-binding profile, creating an additional ETS1/ GABPα site that is sufficient to drive ectopic Shh expression. DNA FISH on E11.5 forelimb and floorplate tissue sections revealed that the Shh-ZRS genomic locus is in a compact chromatin conformation in both Shhexpressing and non-expressing cells. However, I show that the ZRS co-localises with Shh to a significantly greater extent in the distal posterior limb bud and the floorplate compared with cells where Shh is not expressed. This thesis presents novel research into long-range gene regulation during limb development, elucidating the role of chromatin re-organisation and how spatial-specific enhancer activity is determined by opposing sets of binding factors.
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Emilsson, Lina. "Detection of Differentially Expressed Genes in Alzheimer's Disease : Regulator of G-protein Signalling 4: A Novel Mediator of APP Processing." Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis : Univ.-bibl. [distributör], 2005. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-5910.

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Mai, Hans-Jörg [Verfasser], and Petra [Akademischer Betreuer] Bauer. "Analysis of differential protein and gene expression in Arabidopsis thaliana depending on iron supply and the abundance of the central iron uptake regulator FIT (Fer-like Iron Deficiency-induced Transcription Factor) and investigations on possible post-translational modifications of FIT / Hans-Jörg Mai. Betreuer: Petra Bauer." Saarbrücken : Saarländische Universitäts- und Landesbibliothek, 2014. http://d-nb.info/1109790228/34.

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Romero, barrios Natali. "Non-codings RNAs, regulators of gene expression in Arabidopsis thaliana root developmental plasticity Noncoding Transcription by Alternative RNA Polymerases Dynamically Regulates an Auxin-Driven Chromatin Loop Battles and hijacks: noncoding transcription in plants Long noncoding RNA modulates alternative splicing regulators in Arabidopsis Detection of generic differential RNA processing events from RNA-seq data." Thesis, Université Paris-Saclay (ComUE), 2016. http://www.theses.fr/2016SACLS128.

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Les techniques de séquençage à haut-débit développées ces dernières années ont permis d'identifier des milliers d’ARN non-codants et des événements tels que l’épissage ou l’édition. Cette approche est à l’origine d’une meilleure compréhension des mécanismes régulant l'expression des gènes. Les longs ARN non-codants (lncARN) ont ainsi émergé comme des acteurs clés de la régulation de divers processus développementaux. Ils agissent soit directement sous leur forme longue par des interactions lncARN-protéine(s) soit après une étape de maturation qui génère des siARN ou des miARN régulateurs, menant à l’extinction génique par clivage des ARNm, la répression de la traduction ou en entrainant des modifications épigénétiques (ADN/chromatine) de leurs cibles. L’objectif de cette thèse était d’élucider les mécanismes d'action de lncARNs dans le développement de la plante. J'ai contribué à l'analyse de l'action du lncARN APOLO dans la régulation de la topologie de la chromatine chez Arabidopsis thaliana. Ensuite, j’ai concentré mes efforts sur le lncARN ASCO (Alternative Splicing COmpetitor) qui interagit avec les protéines NSRs (Nuclear Speckles RNA-binding Proteins) et participent au patron d’épissage de certains gènes cibles. Lors d’un traitement par l’auxine, NSRb est induit alors qu’ASCO est réprimé dans les racines. Le même type de traitement, chez le double mutant nsra/b et les lignées surexprimant ASCO, entraine déficience partielle dans la formation des racines latérales. En utilisant un nouvel outil bio-informatique appelé "RNAprof", nous avons détecté 1885 ARN différentiellement maturés entre le mutant nsra/b et la lignée sauvage traités à l’auxine. Parmi ces gènes, nous avons identifié ARF19, un régulateur clé de la voie de signalisation de l’auxine au cours de l'initiation et le développement de la racine. J’ai démontré qu'ARF19 interagit directement avec les NSRs et qu’il est différentiellement polyadénylé dans le double mutant nsra/b, conduisant à une isoforme plus courte du transcrit ARF19. D’autre part, parmi les gènes dérégulés de manière transcriptionnelle chez le mutant des gènes impliqués dans la signalisation par l’éthylène ont été identifiés. J’ai ensuite montré que plusieurs de ces gènes sont aussi dérégulés dans les plantes mutantes arf19-1 et arf19-2 en réponse à l’auxine, soutenant un rôle d'ARF19 dans la réponse croisée entre l’auxine et l’éthylène. Le gène NSRb est induit par l'éthylène et l'inhibition de la synthèse d'éthylène par l'AVG complémente le phénotype de racine latérale du mutant nsra/b en réponse à l’auxine. De plus, l'AVG et la surexpression d’ASCO augmentent l'accumulation de l’isoforme courte d’ARF19. Cette étude met en avant la capacité du lncARN ASCO à moduler l’épissage par le détournement des NSRs et la capacité des ARN non-codants à moduler l’épissage
In the last years, high-throughput sequencing techniques have made possible to identify thousands of noncoding RNAs and a plethora of different mRNA processing events occurring in higher organisms. This led to a better understanding of different regulatory mechanisms controlling gene expression. Long noncoding RNAs (lncRNAs) are emerging as key players in the regulation of varied developmental processes. They can act directly in a long form by lncRNA-protein interactions or be processed into shorter small si/miRNAs, leading to mRNA cleavage, translational repression or epigenetic DNA/chromatin modification of their targets. In this study, we aim to understand the mechanism of action of lncRNAs in plant development. Initially, I contributed to the analysis of the action of the APOLO lncRNA in chromatin topology regulation. Then, I focused my work on the lncRNA ASCO (Alternative Splicing COmpetitor) that interacts with NSRs (Nuclear Speckles RNA-binding Proteins) to modulate the splicing pattern of NSR-regulated mRNA targets. Auxin treatment induces NSRb and represses ASCO expression in roots. The nsra/b double mutant and ASCO overexpressing lines treated with auxin are partially impaired in lateral root formation. Using a new bioinformatic tool called “RNAprof”, we detected 1885 differential RNA processing events genome-wide in auxin-treated nsra/b mutants compared to WT. Among them, we identified ARF19, a key regulator of auxin signaling in lateral root initiation and development. I demonstrated that ARF19 is directly bound by both NSRs and that in the nsra/b double mutant ARF19 is alternatively polyadenylated leading to a short transcript isoform. Furthermore, among the transcriptionally deregulated genes in the nsra/b mutant plants, I identified an important group related to ethylene response. I further showed that several of these genes are also deregulated in the arf19-1 and arf19-2 mutants plants in response to auxin, supporting a role of ARF19 in the auxin-ethylene crosstalk. NSRb is also induced by ethylene and the inhibition of ethylene synthesis by AVG rescues the nsra/b double mutant lateral root phenotype in response to auxin. Moreover, AVG and ASCO overexpression lead to increased accumulation of the ARF19 short isoform. Altogether, this study shed new light on the role of the lncRNA ASCO in the regulation of RNA processing by hijacking NSRs and the capacity of non-coding RNAs to modulate splicing
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Book chapters on the topic "DIFFERENTIALLY REGULATED GENES"

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Zipporah E, Binita, Kavitha Govarthanan, Pavithra Shyamsunder, and Rama S. Verma. "Expression Profiling of Differentially Regulated Genes in Fanconi Anemia." In Methods in Molecular Biology, 243–58. New York, NY: Springer New York, 2018. http://dx.doi.org/10.1007/978-1-4939-7834-2_12.

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Paro, Renato, Ueli Grossniklaus, Raffaella Santoro, and Anton Wutz. "Genomic Imprinting." In Introduction to Epigenetics, 91–115. Cham: Springer International Publishing, 2021. http://dx.doi.org/10.1007/978-3-030-68670-3_5.

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AbstractA typical cell contains two sets of chromosomes: one that was inherited from the mother, the other from the father. Usually, autosomal alleles are expressed at similar levels from the maternally and paternally inherited chromosomes. This chapter is dedicated to an exception of this rule: the expression of genes that are regulated by genomic imprinting depends on the parental origin of the allele, leading to the non-equivalence of maternal and paternal genomes. Genomic imprinting is a paradigm of epigenetic gene regulation as genetically identical alleles can exist in two expression states within the same nucleus. The imprints marking the parental alleles are established in the parental germline, maintained during the development of the offspring, but reset before they are passed on to the next generation. In mammals, the primary imprint is usually a differentially methylated region at the locus but there are also examples where histone modifications mark the parental alleles. Many imprinted genes play important roles for development and are associated with human disease. Interestingly, genomic imprinting evolved independently in mammals and seed plants and similar mechanisms have been recruited to regulate imprinted expression in the two kingdoms. We will discuss evolutionary constraints that could have led to the evolution of genomic imprinting in these seemingly disparate lineages.
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Paro, Renato, Ueli Grossniklaus, Raffaella Santoro, and Anton Wutz. "Dosage Compensation Systems." In Introduction to Epigenetics, 67–89. Cham: Springer International Publishing, 2021. http://dx.doi.org/10.1007/978-3-030-68670-3_4.

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AbstractThis chapter provides an introduction to chromosome-wide dosage compensation systems. We will examine the evolution of dosage compensation, which is thought to be driven by the appearance of differentiated sex chromosomes. In a subset of species with X chromosomal sex determination or XY sex chromosome systems, expression of X-linked genes is regulated by chromosome-wide modifications that equalize gene expression differences between males and females. The molecular mechanisms of X chromosome-wide dosage compensation have been studied in flies, worms, and mammals. Each of these species uses a distinct dosage compensation strategy with a different molecular mechanism. In the wormCaenorhabditis elegans, gene expression on the two X chromosomes of hermaphrodites is reduced to a level that approximates a single X chromosome in males. The fruit flyDrosophila melanogasterachieves dosage compensation by increased transcription of the single X chromosome in males to a level that is similar to the two X chromosomes in females. Lastly, in mammals, one of the two X chromosomes in female cells is transcriptionally inactive and a single X chromosome is transcribed in both sexes. Studies of dosage compensation systems provide insights into how epigenetic regulation controls gene expression and chromatin organization differentially within a cell.
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Shinomura, Tamayuki, Kazuo Ito, and Magnus Höök. "Differential gene trap: A new strategy for identifying genes regulated during cartilage differentiation." In The Many Faces of Osteoarthritis, 309–11. Basel: Birkhäuser Basel, 2002. http://dx.doi.org/10.1007/978-3-0348-8133-3_32.

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White, Jay A., and Martin Petkovich. "Identification and Cloning of RA-Regulated Genes by mRNA-Differential Display." In Retinoid Protocols, 389–404. Totowa, NJ: Humana Press, 1998. http://dx.doi.org/10.1385/0-89603-438-0:389.

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Misra, Santosh, Malinee Chatthai, Timothy J. Tranbarger, Benjamin S. Forward, and Karia H. Kaukinen. "Differentially Regulated Gene Sets in Douglas Fir Seeds and Somatic Embryos." In Somatic Cell Genetics and Molecular Genetics of Trees, 197–204. Dordrecht: Springer Netherlands, 1996. http://dx.doi.org/10.1007/978-94-011-3983-0_27.

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Kirov, Stefan, Ruiru Ji, Jing Wang, and Bing Zhang. "Functional Annotation of Differentially Regulated Gene Set Using WebGestalt: A Gene Set Predictive of Response to Ipilimumab in Tumor Biopsies." In Gene Function Analysis, 31–42. Totowa, NJ: Humana Press, 2013. http://dx.doi.org/10.1007/978-1-62703-721-1_3.

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Nehls, U., A. Bock, and R. Hampp. "Differential expression of hexose-regulated fungal genes within Amanita muscaria/Populus tremula × tremuloides ectomycorrhizas." In Plant Nutrition, 650–51. Dordrecht: Springer Netherlands, 2001. http://dx.doi.org/10.1007/0-306-47624-x_315.

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Blok, Leen J., M. Vijay Kumar, and Donald J. Tindall. "Isolation of Differentially Expressed cDNAs from Prostate Cancer Cell Lines Using Differential Display PCR: Identification of an Androgen-Regulated Gene." In Hormonal Carcinogenesis II, 252–59. New York, NY: Springer New York, 1996. http://dx.doi.org/10.1007/978-1-4612-2332-0_28.

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Karpinski, Stanislaw, and Gunnar Wingsle. "Glutathione Regulates Differentially Expression of Genes Encoding Glutathione Reductase and CuZn-Superoxide Dismutase in Scots Pine Needles." In Photosynthesis: from Light to Biosphere, 2507–10. Dordrecht: Springer Netherlands, 1995. http://dx.doi.org/10.1007/978-94-009-0173-5_589.

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Conference papers on the topic "DIFFERENTIALLY REGULATED GENES"

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Bandyopadhyay, Nirmalya, Manas Somaiya, Sanjay Ranka, and Tamer Kahveci. "Identifying differentially regulated genes." In 2011 IEEE 1st International Conference on Computational Advances in Bio and Medical Sciences (ICCABS). IEEE, 2011. http://dx.doi.org/10.1109/iccabs.2011.5729877.

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Teixeira, Lívia, Izabela Conceição, Paulo Caramelli, Marcelo Luizon, and Karina Gomes. "ALZHEIMER’S DISEASE AND TYPE 2 DIABETES MELLITUS: COMMON MIRNAS, GENES AND REGULATORY BIOLOGICAL PATHWAYS." In XIII Meeting of Researchers on Alzheimer's Disease and Related Disorders. Zeppelini Editorial e Comunicação, 2021. http://dx.doi.org/10.5327/1980-5764.rpda066.

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Background: The increased incidence of Type 2 Diabetes Mellitus (T2DM) in the 21st century, along with the higher risk of developing Alzheimer’s disease (AD) in diabetic patients have stimulated the search for pathways that link glycemic disorders to neurodegeneration. MicroRNAs (miRNAs) are non-coding RNAs that play key roles in regulating gene expression. Objective: To identify miRNAs, genes and their regulatory pathways in common in AD and T2DM. Methods: Literature search was carried out to find miRNAs commonly expressed in AD and T2DM. MiRTarBase database was used to provide experimentally validated information on the interactions between miRNAs and their target genes. The functional enrichment of molecular pathways differentially regulated by these miRNAs was performed using EnrichR with Reactome gene set annotation. Results: We found six circulating miRNAs commonly expressed in both diseases (hsa-mir-21; hsamir-103a-1; hsa-mir-103a-2; hsa-mir-107; hsa-mir-146a and hsa-mir-144), which regulate 129 target genes. The common pathways between AD and T2DM were related to inflammatory mediators, cell death and axon formation signalling with p-adjust <10-5. Conclusion: Our study provides evidence that AD and T2DM share common pathophysiological mechanisms and regulators miRNAs, and suggests miRNAs as potential markers related to both diseases.
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Zhang, Xin, Erika Gonzalez Rodriguez, Melanie Markmann, Prajakta Oak, and Anne Hilgendorff. "Expression profiling of genes differentially regulated under hyperoxia andmechanical ventilation in mouse model of neonatal chronic lung disease." In ERS International Congress 2019 abstracts. European Respiratory Society, 2019. http://dx.doi.org/10.1183/13993003.congress-2019.pa4113.

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Li, Y., C. Wang, Y. Chang, C. Chen, and Y. Chen. "Differentially expressed FOXO1, NFE2L2 and NFKB1 mRNAs are associated with differentially regulated corona- and influenza viral receptor genes and Toll-like receptor pathway genes in human bronchial epithelial cells under hyperbaric oxygen exposure." In ERS International Congress 2022 abstracts. European Respiratory Society, 2022. http://dx.doi.org/10.1183/13993003.congress-2022.168.

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Chen, Jianan, Yutaka Amemiya, Gregory Kuling, Homa Fashandi, Yulia Yerofeyeva, Heba Hussein, Elzbieta Slodkowska, et al. "Abstract P6-10-12: Texture heterogeneity of breast tumour in magnetic resonance imaging can be explained by differentially regulated genes." In Abstracts: 2019 San Antonio Breast Cancer Symposium; December 10-14, 2019; San Antonio, Texas. American Association for Cancer Research, 2020. http://dx.doi.org/10.1158/1538-7445.sabcs19-p6-10-12.

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Driscoll, Tristan P., Su-Jin Heo, and Robert L. Mauck. "Dynamic Tensile Loading and Altered Cell Contractility Modulate Nuclear Deformation and Cytoskeletal Connectivity." In ASME 2012 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2012. http://dx.doi.org/10.1115/sbc2012-80550.

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Effective use of progenitor cells in orthopaedic tissue engineering will require a thorough understanding of the mechanisms by which forces are transmitted and sensed, and how these change with differentiation. Nesprins are a family of structural proteins that partially localize to the nuclear envelope where they interact with both cytoskeletal and nucleoskeletal proteins [1]. At their C-terminus, nesprins interact through a KASH domain with proteins of the nuclear membrane, including SUN and Lamin A/C [1]. Multiple isoforms of the 4 nesprin genes are produced by alternative transcriptional initiation, translation and splicing. Specifically, nesprin 1 and nesprin 2 giant contain an N-terminal calponin homology domain (CH) that binds to and co-localizes with F-actin [2]. These nesprins are necessary for transmission of stress to the nucleus and are also differentially regulated with myogenesis, neurogenesis and adipogenesis [3,4]. We previously demonstrated that addition of TGF-3 induced nuclear Lamin A/C reorganization and nuclear stiffening in mesenchymal stem cells (MSCs), along with increased cell contractility and altered accumulation of smaller nesprin isoforms [5,6]. This study sought to determine the importance of contractility in transmission of force to the nucleus and the effect of dynamic loading on the expression of the giant nesprin isoforms.
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Maul, Timothy M., Douglas W. Chew, Alejandro Nieponice, and David A. Vorp. "Mesenchymal Progenitor Cells Differentially Respond to Mechanical Stimulation: Morphology, Proliferation, Gene and Protein Expression." In ASME 2007 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2007. http://dx.doi.org/10.1115/sbc2007-175994.

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Mechanical stimulation has been shown to regulate gene and protein expression in many cell types, including stem cells. Cyclic strain has been previously shown by our laboratory and others [1, 2] to regulate smooth muscle gene and protein expression in mesenchymal progenitor cells (MPCs). From these and other results [3], we hypothesize that the differentiated phenotype of MPCs may be controlled by the appropriate type, magnitude, and frequency of mechanical stimulation. We describe here the differential response of MPCs to three mechanical stimuli — cyclic strain, cyclic hydrostatic pressure, and laminar shear stress — over a range of magnitudes and frequencies that are consistent with the cardiovascular system.
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Wilson, Timothy M., Larsson Omberg, Neil R. Hackett, and Ronald G. Crystal. "Genetic Variability Can Differentially Regulate Genes In Airway Epithelium And Alveolar Macrophages." In American Thoracic Society 2010 International Conference, May 14-19, 2010 • New Orleans. American Thoracic Society, 2010. http://dx.doi.org/10.1164/ajrccm-conference.2010.181.1_meetingabstracts.a6594.

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Zaliz, Rocio Romero, Oscar Harari, Cristina Rubio Escudero, and Igor Zwir. "Identifying the promoter features governing differential kinetics of co-regulated genes using fuzzy expressions." In 2007 IEEE International Fuzzy Systems Conference. IEEE, 2007. http://dx.doi.org/10.1109/fuzzy.2007.4295532.

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Camilleri, Emily, Carlos Aya-Bonilla, Jamie Nourse, Philip J. Brown, Alison H. Banham, Paula Marlton, Maher K. Gandhi, and Lyn R. Griffiths. "Abstract B38: FOXP1 truncated isoforms differentially regulate target genes in diffuse large B cell lymphoma." In Abstracts: AACR Special Conference on Tumor Immunology: Multidisciplinary Science Driving Basic and Clinical Advances; December 2-5, 2012; Miami, FL. American Association for Cancer Research, 2013. http://dx.doi.org/10.1158/1538-7445.tumimm2012-b38.

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Reports on the topic "DIFFERENTIALLY REGULATED GENES"

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Wan, Yihong, and Steven K. Nordeen. The Identification of Genes Differentially Regulated by Progestins and Glucocorticoids in Human Breast Cancer Cells. Fort Belvoir, VA: Defense Technical Information Center, July 2002. http://dx.doi.org/10.21236/ada406196.

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Wan, Yigong, and Steven K. Nordeen. The Identification of Genes Differentially Regulated by Progestins and Glucocorticords in Human Breast Cancer Cells. Fort Belvoir, VA: Defense Technical Information Center, July 2000. http://dx.doi.org/10.21236/ada383648.

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Arazi, Tzahi, Vivian Irish, and Asaph Aharoni. Micro RNA Targeted Transcription Factors for Fruit Quality Improvement. United States Department of Agriculture, July 2008. http://dx.doi.org/10.32747/2008.7592651.bard.

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Fruits are unique to flowering plants and represent an important component of human and animal diets. Development and maturation of tomato fruit is a well-programmed process, and yet, only a limited number of factors involved in its regulation have been characterized. Micro-RNAs (miRNAs) are small, endogenous RNAs that regulate gene expression in animals and plants. Plant miRNAs have a vital role in the generation of plant forms through post-transcriptional regulation of the accumulation of developmental regulators, especially transcription factors. Recently, we and others have demonstrated that miRNAs and other type of small RNAs are expressed in tomato fruit, and target putative transcription factors during its development and maturation. The original objectives of the approved proposal were: 1. To identify fruit miRNA transcription factor target genes through a bioinformatic approach. 2. To identify fruit miRNA transcription factor target genes up-regulated in tomato Dicer-like 1 silenced fruit. 3. To establish the biological functions of selected transcription factors and examine their utility for improving fleshy fruit quality trait. This project was approved by BARD as a feasibility study to allow initial experiments to peruse objective 2 as described above in order to provide initial evidence that miRNAs do play a role in fruit development. The approach planned to achieve objective 2, namely to identify miRNA transcription factor targets was to clone and silence the expression of a tomato DCL1 homolog in different stages of fruit development and examine alterations to gene expression in such a fruit in order to identify pathways and target genes that are regulated by miRNA via DCL1. In parallel, we characterized two transcription factors that are regulated by miRNAs in the fruit. We report here on the cloning of tomato DCL1 homolog, characterization of its expression in fruit flesh and peel of wild type and ripening mutants and generation of transgenic plants that silence SlDCL1 specifically in the fruit. Our results suggest that the tomato homolog of DCL1, which is the major plant enzyme involved in miRNA biogenesis, is present in fruit flesh and peel and differentially expressed during various stages of fruit development. In addition, its expression is altered in ripening mutants. We also report on the cloning and expression analysis of Sl_SBP and Sl_ARF transcription factors, which serve as targets of miR157 and miR160, respectively. Our data suggest that Sl_SBP levels are highest during fruit ripening supporting a role for this gene in that process. On the other hand Sl_ARF is strongly expressed in green fruit up to breaker indicating a role for that gene at preripening stage which is consistent with preliminary in_situ analyses that suggest expression in ovules of immature green fruit. The results of this feasibility study together with our previous results that miRNAs are expressed in the fruit indeed provide initial evidence that these regulators and their targets play roles in fruit development and ripening. These genes are expected to provide novel means for genetic improvement of tomato fleshy fruit.
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Sadka, Avi, Mikeal L. Roose, and Yair Erner. Molecular Genetic Analysis of Citric Acid Accumulation in Citrus Fruit. United States Department of Agriculture, March 2001. http://dx.doi.org/10.32747/2001.7573071.bard.

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The acid content of the juice sac cells is a major determinant of maturity and fruit quality in citrus. Many citrus varieties accumulate acid in concentrations that exceed market desires, reducing grower income and consumer satisfaction. Pulp acidity is thought to be dependent on two mechanisms: the accumulation of citric acid in the vacuoles of the juice sac cells, and acidification of the vacuole. The major aim of the project was to direct effort toward understanding the mechanism of citric acid accumulation in the fruit. The following objectives were suggested: Measure the activity of enzymes likely to be involved in acid accumulation and follow their pattern of expression in developing fruit (Sadka, Erner). Identify and clone genes which are associated with high and low acid phenotypes and with elevated acid level (Roose, Sadka, Erner). Convert RAPD markers that map near a gene that causes low acid phenotype to specific co dominant markers (Roose). Use genetic co segregation to test whether specific gene products are responsible for low acid phenotype (Roose and Sadka). Objective 1 was fully achieved. Most of the enzymes of organic acid metabolism were cloned from lemon pulp. Their expression was studied during fruit development in low and high acid varieties. The activity and expression of citrate synthase, aconitase and NADP-isocitrate dehydrogenase (IDH) were studied in detail. The role that each enzyme plays in acid accumulation and decline was evaluated. As a result, a better understanding of the metabolic changes that contribute to acid accumulation was achieved. It was found that the activity of the mitochondrial aconitase is greatly reduced early in high-acid fruits, but not in acidless ones, suggesting that this enzyme plays an important role in acid accumulation. In addition, it was demonstrated that increases in the cytosolic forms of aconitase and NADP-IDH towards fruit maturation play probably a major role in acid decline. Our studies also demonstrated that the two mechanisms that contribute to fruit acidity, vacuolar acidification and citric acid accumulation, are independent, although they are tightly co-regulated. Additional, we demonstrated that sodium arsenite, which reduce fruit acidity, causes a transient inhibition in the activity of citrate synthase, but an induction in the gene expression. This part of the work has resulted in 4 papers. Objective 3 was also fully achieved. Using bulked segregant analysis, three random amplified polymorphic DNA (RAPD) markers were identified as linked to acitric, a gene controlling the acidless phenotype of pummelo 2240. One of them, which mapped 1.2 cM from acitric was converted into sequence characterized amplified region (SCAR marker, and into co dominant restriction length polymorphism (RFLP) marker. These markers were highly polymorphic among 59 citrus accessions, and therefore, they should be useful for selecting seedling progeny heterozygous for acitric in nearly all crosses between pummelo 2240 and other citrus genotypes. This part of the project resulted in one paper. Objective 4 was also fully achieved. Clones isolated by the Israeli group were sent to the American laboratory for co segregation analysis. However, none of them seemed to co segregate with the low acid phenotype. Both laboratories invested much effort in achieving the goals of Objective 2, namely the isolation of genes that are elevated in expression in low and high acid phenotypes, and in tissue cultures treated with arsenite (a treatment which reduces fruit acidity). However, conventional differential display and restriction fragment differential display analyses could not identify any differentially expressed genes. The isolation of such genes was the major aim of a continuation project, which was recently submitted.
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Whitham, Steven A., Amit Gal-On, and Tzahi Arazi. Functional analysis of virus and host components that mediate potyvirus-induced diseases. United States Department of Agriculture, March 2008. http://dx.doi.org/10.32747/2008.7591732.bard.

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The mechanisms underlying the development of symptoms in response to virus infection remain to be discovered in plants. Insight into symptoms induced by potyviruses comes from evidence implicating the potyviral HC-Pro protein in symptom development. In particular, recent studies link the development of symptoms in infected plants to HC-Pro's ability to interfere with small RNA metabolism and function in plant hosts. Moreover, mutation of the highly conserved FRNK amino acid motif to FINK in the HC-Pro of Zucchini yellow mosaic virus (ZYMV) converts a severe strain into an asymptomatic strain, but does not affect virus accumulation in cucurbit hosts. The ability of this FINK mutation to uncouple symptoms from virus accumulation creates a unique opportunity to study symptom etiology, which is usually confounded by simultaneous attenuation of both symptoms and virus accumulation. Our goal was to determine how mutations in the conserved FRNK motif affect host responses to potyvirus infection in cucurbits and Arabidopsis thaliana. Our first objective was to define those amino acids in the FRNK motif that are required for symptoms by mutating the FRNK motif in ZYMV and Turnip mosaic virus (TuMV). Symptom expression and accumulation of resulting mutant viruses in cucurbits and Arabidopsis was determined. Our second objective was to identify plant genes associated with virus disease symptoms by profiling gene expression in cucurbits and Arabidopsis in response to mutant and wild type ZYMV and TuMV, respectively. Genes from the two host species that are differentially expressed led us to focus on a subset of genes that are expected to be involved in symptom expression. Our third objective was to determine the functions of small RNA species in response to mutant and wild type HC-Pro protein expression by monitoring the accumulation of small RNAs and their targets in Arabidopsis and cucurbit plants infected with wild type and mutant TuMV and ZYMV, respectively. We have found that the maintenance of the charge of the amino acids in the FRNK motif of HC-Pro is required for symptom expression. Reduced charge (FRNA, FRNL) lessen virus symptoms, and maintain the suppression of RNA silencing. The FRNK motif is involved in binding of small RNA species including microRNAs (miRNA) and short interfering RNAs (siRNA). This binding activity mediated by the FRNK motif has a role in protecting the viral genome from degradation by the host RNA silencing system. However, it also provides a mechanism by which the FRNK motif participates in inducing the symptoms of viral infection. Small RNA species, such as miRNA and siRNA, can regulate the functions of plant genes that affect plant growth and development. Thus, this binding activity suggests a mechanism by which ZYMVHC-Pro can interfere with plant development resulting in disease symptoms. Because the host genes regulated by small RNAs are known, we have identified candidate host genes that are expected to play a role in symptoms when their regulation is disrupted during viral infections. As a result of this work, we have a better understanding of the FRNK amino acid motif of HC-Pro and its contribution to the functions of HC-Pro, and we have identified plant genes that potentially contribute to symptoms of virus infected plants when their expression becomes misregulated during potyviral infections. The results set the stage to establish the roles of specific host genes in viral pathogenicity. The potential benefits include the development of novel strategies for controlling diseases caused by viruses, methods to ensure stable expression of transgenes in genetically improved crops, and improved potyvirus vectors for expression of proteins or peptides in plants.
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Friedman, Haya, Julia Vrebalov, and James Giovannoni. Elucidating the ripening signaling pathway in banana for improved fruit quality, shelf-life and food security. United States Department of Agriculture, October 2014. http://dx.doi.org/10.32747/2014.7594401.bard.

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Background : Banana being a monocot and having distinct peel and pulp tissues is unique among the fleshy fruits and hence can provide a more comprehensive understanding of fruit ripening. Our previous research which translated ripening discoveries from tomato, led to the identification of six banana fruit-associated MADS-box genes, and we confirmed the positive role of MaMADS1/2 in banana ripening. The overall goal was to further elucidate the banana ripening signaling pathway as mediated by MADS-boxtranscriptional regulators. Specific objectives were: 1) characterize transcriptional profiles and quality of MaMADS1/2 repressed fruit; 2) reveal the role of additional MaMADSgenes in ripening; 3) develop a model of fruit MaMADS-box mode of action; and 4) isolate new components of the banana ripening signaling pathway. Major conclusion: The functions of the banana MaMADS1-5 have been examined by complimenting the rinor the TAGL1-suppressed lines of tomato. Only MaMADS5 exhibited partial complementation of TAGL1-suppressed and rinlines, suggesting that while similar genes play corresponding roles in ripening, evolutionary divergence makes heterologous complementation studies challenging. Nevertheless, the partial complementation of tomato TAGL1-surpessed and rinlines with MaMADS5 suggests this gene is likely an important ripening regulator in banana, worthy of further study. RNA-seqtranscriptome analysis during ripening was performed on WT and MaMADS2-suppressed lines revealing additional candidate genes contributing to ripening control mechanisms. In summary, we discovered 39 MaMADS-box genes in addition to homologues of CNR, NOR and HB-1 expressed in banana fruits, and which were shown in tomato to play necessary roles in ripening. For most of these genes the expression in peel and pulp was similar. However, a number of key genes were differentially expressed between these tissues indicating that the regulatory components which are active in peel and pulp include both common and tissue-specific regulatory systems, a distinction as compared to the more uniform tomato fruit pericarp. Because plant hormones are well documented to affect fruit ripening, the expressions of genes within the auxin, gibberellin, abscisic acid, jasmonic acid, salicylic and ethylene signal transduction and synthesis pathways were targeted in our transcriptome analysis. Genes’ expression associated with these pathways generally declined during normal ripening in both peel and pulp, excluding cytokinin and ethylene, and this decline was delayed in MaMADS2-suppressed banana lines. Hence, we suggest that normal MaMADS2 activity promotes the observed downward expression within these non-ethylene pathways (especially in the pulp), thus enabling ripening progression. In contrast, the expressions of ACSand ACOof the ethylene biosynthesis pathway increase in peel and pulp during ripening and are delayed/inhibited in the transgenic bananas, explaining the reduced ethylene production of MaMADS2-suppressed lines. Inferred by the different genes’ expression in peel and pulp of the gibberellins, salicylic acid and cytokinins pathways, it is suggested that hormonal regulation in these tissues is diverse. These results provide important insights into possible avenues of ripening control in the diverse fruit tissues of banana which was not previously revealed in other ripening systems. As such, our transcriptome analysis of WT and ripening delayed banana mutants provides a starting point for further characterization of ripening. In this study we also developed novel evidence that the cytoskeleton may have a positive role in ripening as components of this pathway were down-regulated by MaMADS2 suppression. The mode of cytoskeleton involvement in fruit ripening remains unclear but presents a novel new frontier in ripening investigations. In summary, this project yielded functional understanding of the role and mode of action of MaMADS2 during ripening, pointing to both induction of ethylene and suppression of non-ethylene hormonal singling pathways. Furthermore, our data suggest important roles for cytoskeleton components and MaMADS5 in the overall banana ripening control network. Implications: The project revealed new molecular components/genes involved in banana ripening and refines our understanding of ripening responses in the peel and pulp tissues of this important species. This information is novel as compared to that derived from the more uniform carpel tissues of other highly studied ripening systems including tomato and grape. The work provides specific target genes for potential modification through genetic engineering or for exploration of useful genetic diversity in traditional breeding. The results from the project might point toward improved methods or new treatments to improve banana fruit storage and quality.
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7

Delmer, Deborah P., and Prem S. Chourey. The Importance of the Enzyme Sucrose Synthase for Cell Wall Synthesis in Plants. United States Department of Agriculture, October 1994. http://dx.doi.org/10.32747/1994.7568771.bard.

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The goal of this work was to understand the role of the enzyme sucrose synthase (SuSy) in synthesis of cellulose and callose in plants. The work resulting from the this grant leads to a number of conclusions. SuSy clearly plays diverse roles in carbon metabolism. It can associate with the plasma membrane of cells undergoing rapid cellulose deposition, such as cotton fibers, developing maize endosperm, gravistimulated pulvini, and transfer cells of the cotton seed. It is also concentrated at sites of high callose deposition (tapetal cells; cell plates). When SuSy levels are lowered by mutation or by anti-sense technology, cell walls undergo degeneration (maize endosperm) and show reduced levels of cellulose (potato tubers). In sum, our evidence has very much strengthened the concept that SuSy does function in the plasma membrane to channel carbon from sucrose via UDP-glucose to glucan synthase complexes. Soluble SuSy also clearly plays a role in providing carbon for starch synthesis and respiration. Surprisingly, we found that the cotton seed is one unique case where SuSy apparently does not play a role in starch synthesis. Current evidence in sum suggests that no specific SuSy gene encodes the membrane-associated form, although in maize the SS 1 form of SuSy may be most important for cell wall synthesis in the early stages of endosperm development. Work is still in progress to determine what does control membrane localization - and the current evidence we have favors a role for Ca2+, and possibly also protein phosphorylation by differentially regulated protein kinases. Finally, we have discovered for the first time, a major new family of genes that encode the catalytic subunit of the cellulose synthase of plants - a result that has been widely cited and opens many new approaches for the study of this important plant function.
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8

Steffens, John C., and Eithan Harel. Polyphenol Oxidases- Expression, Assembly and Function. United States Department of Agriculture, January 1995. http://dx.doi.org/10.32747/1995.7571358.bard.

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Polyphenol oxidases (PPOs) participate in the preparation of many plant products on the one hand and cause considerable losses during processing of plant products on the other hand. However, the physiological functions of plant PPO were still a subject of controversy at the onset of the project. Preliminary observations that suggested involvement of PPOs in resistance to herbivores and pathogens held great promise for application in agriculture but required elucidation of PPO's function if modulation of PPO expression is to be considered for improving plant protection or storage and processing of plant products. Suggestions on a possible role of PPO in various aspects of chloroplast metabolism were also relevant in this context. The characterization of plant PPO genes opened a way for achieving these goals. We reasoned that "understanding PPO targeting and routing, designing ways to manipulate its expression and assessing the effects of such modifications will enable determination of the true properties of the enzyme and open the way for controlling its activity". The objective of the project was to "obtain an insight into the function and biological significance of PPOs" by examining possible function(s) of PPO in photosynthesis and plant-pest interactions using transgenic tomato plants; extending our understanding of PPO routing and assembly and the mechanism of its thylakoid translocation; preparing recombinant PPOs for use in import studies, determination of the genuine properties of PPOs and understanding its assembly and determining the effect of PPO's absence on chloroplast performance. Results obtained during work on the project made it necessary to abandon some minor objectives and devote the effort to more promising topics. Such changes are mentioned in the 'Body of the report' which is arranged according to the objectives of the original proposal. The complex expression pattern of tomato PPO gene family was determined. Individual members of the family are differentially expressed in various parts of the plant and subjected to developmentally regulated turnover. Some members are differentially regulated also by pathogens, wounding and chemical wound signals. Wounding systemically induces PPO activity and level in potato. Only tissues that are developmentally competent to express PPO are capable of responding to the systemic wounding signal by increased accumulation of PPO mRNA. Down regulation of PPO genes causes hyper susceptibility to leaf pathogens in tomato while over expression regulation of PPO expression in tomato plants is their apparent increased tolerance to drought. Both the enhanced disease resistance conferred by PPO over expression and the increased stress tolerance due to down regulation can be used in the engineering of improved crop plants. Photosynthesis rate and variable fluorescence measurements in wild type, and PPO-null and over expressing transgenic tomato lines suggest that PPO does not enable plants to cope better with stressful high light intensities or reactive oxygen species. Rather high levels of the enzyme aggravate the damage caused under such conditions. Our work suggests that PPO's primary role is in defending plants against pathogens and herbivores. Jasmonate and ethylene, and apparently also salicylate, signals involved in responses to wounding and defense against herbivores and pathogens, enhance markedly and specifically the competence of chloroplasts to import and process pPPO. The interaction of the precursor with thylakoid membranes is primarily affected. The routing of PPO shows other unusual properties: stromal processing occurs in two sites, resulting in intermediates that are translocated across thylakoids by two different mechanisms - a DpH- and a Sec-dependent one. It is suggested that the dual pattern of processing and routing constitutes a'fail safe' mechanism, reflecting the need for a rapid and flexible response to defense challenges. Many of the observations described above should be taken into consideration when manipulation of PPO expression is contemplated for use in crop improvement.
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9

Prusky, Dov, Nancy P. Keller, and Amir Sherman. global regulation of mycotoxin accumulation during pathogenicity of Penicillium expansum in postharvest fruits. United States Department of Agriculture, January 2014. http://dx.doi.org/10.32747/2014.7600012.bard.

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Background to the topic- Penicilliumas a postharvest pathogen and producer of the mycotoxin PAT. Penicilliumspp. are destructive phytopathogens, capable of causing decay in many deciduous fruits, during postharvest handling and storage; and the resulting losses can amount to 10% of the stored produce and the accumulation of large amounts of the mycotoxinpatulin. The overall goal of this proposal is to identify critical host and pathogen factors that modulate P. expansummycotoxin genes and pathways which are required for PAT production and virulence. Our preliminary results indicated that gluconic acid are strongly affecting patulin accumulation during colonization. P. expansumacidifies apple fruit tissue during colonization in part through secretion of gluconic acid (GLA). Several publications suggested that GLA accumulation is an essential factor in P. expansumpathogenicity. Furthermore, down regulation of GOX2 significantly reduced PAT accumulation and pathogenicity. PAT is a polyketide and its biosynthesis pathway includes a 15-gene cluster. LaeA is a global regulator of mycotoxin synthesis. It is now known that patulin synthesis might be subjected to LaeA and sometimes by environmental sensing global regulatory factors including the carbon catabolite repressor CreA as well as the pH regulator factor PacC and nitrogen regulator AreA. The mechanisms by which LaeA regulates patulin synthesis was not fully known and was part of our work. Furthermore, the regulatory system that controls gene expression in accordance with ambient pH was also included in our work. PacC protein is in an inactive conformation and is unable to bind to the promoter sites of the target genes; however, under alkaline growth conditions activated PacC acts as both an activator of alkaline-expressed genes and a repressor of acid-expressed genes. The aims of the project- This project aims to provide new insights on the roles of LaeA and PacC and their signaling pathways that lead to GLA and PAT biosynthesis and pathogenicity on the host. Specifically, our specific aims were: i) To elucidate the mechanism of pH-controlled regulation of GLA and PAT, and their contribution to pathogenesis of P. expansum. We are interested to understanding how pH and/or GLA impact/s under PacC regulation affect PAT production and pathogenesis. ii) To characterize the role of LaeA, the global regulator of mycotoxin production, and its effect on PAT and PacC activity. iii) To identify the signaling pathways leading to GLA and PAT synthesis. Using state- of-the-art RNAseq technologies, we will interrogate the transcriptomes of laeAand pacCmutants, to identify the common signaling pathways regulating synthesis of both GLA and PAT. Major conclusions, solutions, achievements- In our first Aim our results demonstrated that ammonia secreted at the leading edge of the fungal colony induced transcript activation of the global pH modulator PacC and PAT accumulation in the presence of GLA. We assessed these parameters by: (i) direct exogenous treatment of P. expansumgrowing on solid medium; (ii) direct exogenous treatment on colonized apple tissue; (iii) growth under self-ammonia production conditions with limited carbon; and (iv) analysis of the transcriptional response to ammonia of the PAT biosynthesis cluster. Ammonia induced PAT accumulation concurrently with the transcript activation of pacCand PAT biosynthesis cluster genes, indicating the regulatory effect of ammonia on pacCtranscript expression under acidic conditions. Transcriptomic analysis of pH regulated processes showed that important genes and BARD Report - Project 4773 Page 2 of 10 functionalities of P. expansumwere controlled by environmental pH. The differential expression patterns of genes belonging to the same gene family suggest that genes were selectively activated according to their optimal environmental conditions to enable the fungus to cope with varying conditions and to make optimal use of available enzymes. Concerning the second and third Aims, we demonstrated that LaeA regulates several secondary metabolite genes, including the PAT gene cluster and concomitant PAT synthesis invitro. Virulence studies of ΔlaeAmutants of two geographically distant P. expansumisolates (Pe-21 from Israel and Pe-T01 from China) showed differential reduction in disease severity in freshly harvested fruit ranging from no reduction for Ch-Pe-T01 strains in immature fruit to 15–25% reduction for both strains in mature fruit, with the ΔlaeAstrains of Is-Pe-21 always showing a greater loss in virulence. Results suggest the importance of LaeA regulation of PAT and other secondary metabolites on pathogenicity. Our work also characterized for the first time the role of sucrose, a key nutritional factor present in apple fruit, as a negative regulator of laeAexpression and consequent PAT production in vitro. This is the first report of sugar regulation of laeAexpression, suggesting that its expression may be subject to catabolite repression by CreA. Some, but not all of the 54 secondary metabolite backbone genes in the P. expansumgenome, including the PAT polyketide backbone gene, were found to be regulated by LaeA. Together, these findings enable for the first time a straight analysis of a host factor that potentially activates laeAand subsequent PAT synthesis.
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10

Ohad, Nir, and Robert Fischer. Regulation of Fertilization-Independent Endosperm Development by Polycomb Proteins. United States Department of Agriculture, January 2004. http://dx.doi.org/10.32747/2004.7695869.bard.

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Arabidopsis mutants that we have isolated, encode for fertilization-independent endosperm (fie), fertilization-independent seed2 (fis2) and medea (mea) genes, act in the female gametophyte and allow endosperm to develop without fertilization when mutated. We cloned the FIE and MEA genes and showed that they encode WD and SET domain polycomb (Pc G) proteins, respectively. Homologous proteins of FIE and MEA in other organisms are known to regulate gene transcription by modulating chromatin structure. Based on our results, we proposed a model whereby both FIE and MEA interact to suppress transcription of regulatory genes. These genes are transcribed only at proper developmental stages, as in the central cell of the female gametophyte after fertilization, thus activating endosperm development. To test our model, the following questions were addressed: What is the Composition and Function of the Polycomb Complex? Molecular, biochemical, genetic and genomic approaches were offered to identify members of the complex, analyze their interactions, and understand their function. What is the Temporal and Spatial Pattern of Polycomb Proteins Accumulation? The use of transgenic plants expressing tagged FIE and MEA polypeptides as well as specific antibodies were proposed to localize the endogenous polycomb complex. How is Polycomb Protein Activity Controlled? To understand the molecular mechanism controlling the accumulation of FIE protein, transgenic plants as well as molecular approaches were proposed to determine whether FIE is regulated at the translational or posttranslational levels. The objectives of our research program have been accomplished and the results obtained exceeded our expectation. Our results reveal that fie and mea mutations cause parent-of-origin effects on seed development by distinct mechanisms (Publication 1). Moreover our data show that FIE has additional functions besides controlling the development of the female gametophyte. Using transgenic lines in which FIE was not expressed or the protein level was reduced during different developmental stages enabled us for the first time to explore FIE function during sporophyte development (Publication 2 and 3). Our results are consistent with the hypothesis that FIE, a single copy gene in the Arabidopsis genome, represses multiple developmental pathways (i.e., endosperm, embryogenesis, shot formation and flowering). Furthermore, we identified FIE target genes, including key transcription factors known to promote flowering (AG and LFY) as well as shoot and leaf formation (KNAT1) (Publication 2 and 3), thus demonstrating that in plants, as in mammals and insects, PcG proteins control expression of homeobox genes. Using the Yeast two hybrid system and pull-down assays we demonstrated that FIE protein interact with MEA via the N-terminal region (Publication 1). Moreover, CURLY LEAF protein, an additional member of the SET domain family interacts with FIE as well. The overlapping expression patterns of FIE, with ether MEA or CLF and their common mutant phenotypes, demonstrate the versatility of FIE function. FIE association with different SET domain polycomb proteins, results in differential regulation of gene expression throughout the plant life cycle (Publication 3). In vitro interaction assays we have recently performed demonstrated that FIE interacts with the cell cycle regulatory component Retinobalsoma protein (pRb) (Publication 4). These results illuminate the potential mechanism by which FIE may restrain embryo sac central cell division, at least partly, through interaction with, and suppression of pRb-regulated genes. The results of this program generated new information about the initiation of reproductive development and expanded our understanding of how PcG proteins regulate developmental programs along the plant life cycle. The tools and information obtained in this program will lead to novel strategies which will allow to mange crop plants and to increase crop production.
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