Artykuły w czasopismach na temat „Genetic transcription factors”

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1

Keller, Andrew D. "Model genetic circuits encoding autoregulatory transcription factors". Journal of Theoretical Biology 172, nr 2 (styczeń 1995): 169–85. http://dx.doi.org/10.1006/jtbi.1995.0014.

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2

Chua, Gordon. "Systematic genetic analysis of transcription factors to map the fission yeast transcription-regulatory network". Biochemical Society Transactions 41, nr 6 (20.11.2013): 1696–700. http://dx.doi.org/10.1042/bst20130224.

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Mapping transcriptional-regulatory networks requires the identification of target genes, binding specificities and signalling pathways of transcription factors. However, the characterization of each transcription factor sufficiently for deciphering such networks remains laborious. The recent availability of overexpression and deletion strains for almost all of the transcription factor genes in the fission yeast Schizosaccharomyces pombe provides a valuable resource to better investigate transcription factors using systematic genetics. In the present paper, I review and discuss the utility of these strain collections combined with transcriptome profiling and genome-wide chromatin immunoprecipitation to identify the target genes of transcription factors.
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3

Becskei, Attila. "Tuning up Transcription Factors for Therapy". Molecules 25, nr 8 (20.04.2020): 1902. http://dx.doi.org/10.3390/molecules25081902.

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The recent developments in the delivery and design of transcription factors put their therapeutic applications within reach, exemplified by cell replacement, cancer differentiation and T-cell based cancer therapies. The success of such applications depends on the efficacy and precision in the action of transcription factors. The biophysical and genetic characterization of the paradigmatic prokaryotic repressors, LacI and TetR and the designer transcription factors, transcription activator-like effector (TALE) and CRISPR-dCas9 revealed common principles behind their efficacy, which can aid the optimization of transcriptional activators and repressors. Further studies will be required to analyze the linkage between dissociation constants and enzymatic activity, the role of phase separation and squelching in activation and repression and the long-range interaction of transcription factors with epigenetic regulators in the context of the chromosomes. Understanding these mechanisms will help to tailor natural and synthetic transcription factors to the needs of specific applications.
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Fazlollahi, Mina, Ivor Muroff, Eunjee Lee, Helen C. Causton i Harmen J. Bussemaker. "Identifying genetic modulators of the connectivity between transcription factors and their transcriptional targets". Proceedings of the National Academy of Sciences 113, nr 13 (10.03.2016): E1835—E1843. http://dx.doi.org/10.1073/pnas.1517140113.

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Regulation of gene expression by transcription factors (TFs) is highly dependent on genetic background and interactions with cofactors. Identifying specific context factors is a major challenge that requires new approaches. Here we show that exploiting natural variation is a potent strategy for probing functional interactions within gene regulatory networks. We developed an algorithm to identify genetic polymorphisms that modulate the regulatory connectivity between specific transcription factors and their target genes in vivo. As a proof of principle, we mapped connectivity quantitative trait loci (cQTLs) using parallel genotype and gene expression data for segregants from a cross between two strains of the yeast Saccharomyces cerevisiae. We identified a nonsynonymous mutation in the DIG2 gene as a cQTL for the transcription factor Ste12p and confirmed this prediction empirically. We also identified three polymorphisms in TAF13 as putative modulators of regulation by Gcn4p. Our method has potential for revealing how genetic differences among individuals influence gene regulatory networks in any organism for which gene expression and genotype data are available along with information on binding preferences for transcription factors.
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5

Ibrahim, Lara, Jaleh Mesgarzadeh, Ian Xu, Evan T. Powers, R. Luke Wiseman i Michael J. Bollong. "Defining the Functional Targets of Cap‘n’collar Transcription Factors NRF1, NRF2, and NRF3". Antioxidants 9, nr 10 (21.10.2020): 1025. http://dx.doi.org/10.3390/antiox9101025.

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The NRF transcription factors NRF1, NRF2, and NRF3, are a subset of Cap‘n’collar transcriptional regulators which modulate the expression of genes harboring antioxidant-response element (ARE) sequences within their genomic loci. Despite the emerging physiological importance of NRF family members, the repertoire of their genetic targets remains incompletely defined. Here we use RNA-sequencing-based transcriptional profiling and quantitative proteomics to delineate the overlapping and differential genetic programs effected by the three NRF transcription factors. We then create consensus target gene sets regulated by NRF1, NRF2, and NRF3 and define the integrity of these gene sets for probing NRF activity in mammalian cell culture and human tissues. Together, our data provide a quantitative assessment of how NRF family members sculpt proteomes and transcriptomes, providing a framework to understand the critical physiological importance of NRF transcription factors and to establish pharmacologic approaches for therapeutically activating these transcriptional programs in disease.
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6

Sapelnikov, O. V., A. A. Kulikov, O. O. Favorova, N. A. Matveeva, D. I. Cherkashin, O. A. Nikolaeva i R. S. Akchurin. "Genetic, Epigenetic and Transcription Factors in Atrial Fibrillation". Rational Pharmacotherapy in Cardiology 15, nr 3 (6.07.2019): 407–15. http://dx.doi.org/10.20996/1819-6446-2019-15-3-407-415.

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Atrial fibrillation (AF) is one of the most common arrhythmia that occurs in patients with cardiovascular diseases. Congenital forms of AF are quite rare. Many studies have shown that genetic, epigenetic and transcription factors may play an important role in the development and the progression of AF. In our review, studies have been conducted on the identification of mutations in ionic and non-ionic channels, possibly associated with AF. These mutations were found only in isolated groups of patients with AF, and in general, monogenic forms of AF are a rare subtype of the disease. Genomic association studies have helped to identify potential links between single nucleotide polymorphisms and AF. The risk of AF in the general population is likely to be determined by the interaction between environmental factors and many alleles. In recent years, the emergence of a genome-wide associative studies has significantly expanded the understanding of the genetic basis for the inheritance of AF and has led to the emergence of new evidence of the important role of genetic factors in the development of AF, in the risk stratification of AF and the recurrence of AF. Epigenetic factors are also important in AF. Epigenetic therapy aimed at treating a disease through exposure to epigenome is currently under development. A newly emerged area of ablatogenomics includes the use of genetic profiles that allow assessing the likelihood of recurrence of AF after catheter ablation. The results of genetic studies in AF show that, in addition to their role in the appearance of congenital heart pathologies, transcription factors play an important role in the pathogenesis of AF.
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7

Poulat, Francis. "Non-Coding Genome, Transcription Factors, and Sex Determination". Sexual Development 15, nr 5-6 (2021): 295–307. http://dx.doi.org/10.1159/000519725.

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In vertebrates, gonadal sex determination is the process by which transcription factors drive the choice between the testicular and ovarian identity of undifferentiated somatic progenitors through activation of 2 different transcriptional programs. Studies in animal models suggest that sex determination always involves sex-specific transcription factors that activate or repress sex-specific genes. These transcription factors control their target genes by recognizing their regulatory elements in the non-coding genome and their binding motifs within their DNA sequence. In the last 20 years, the development of genomic approaches that allow identifying all the genomic targets of a transcription factor in eukaryotic cells gave the opportunity to globally understand the function of the nuclear proteins that control complex genetic programs. Here, the major transcription factors involved in male and female vertebrate sex determination and the genomic profiling data of mouse gonads that contributed to deciphering their transcriptional regulation role will be reviewed.
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8

Schödel, Johannes, David Robert Mole i Peter John Ratcliffe. "Pan-genomic binding of hypoxia-inducible transcription factors". Biological Chemistry 394, nr 4 (1.04.2013): 507–17. http://dx.doi.org/10.1515/hsz-2012-0351.

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Abstract Hypoxia-inducible transcription factors (HIFs) mediate the cellular response to hypoxia. HIF-DNA binding triggers a transcriptional program that acts to both restore oxygen homeostasis and adapt cells to low oxygen availability. In this context, HIF is centrally involved in many physiologic and pathophysiological processes such as development, high altitude adaptation, ischemic disease, inflammation, and cancer. The recent development of chromatin immunoprecipitation coupled to genome-wide DNA sequence analysis allows the position and extent of HIF binding to DNA to be characterized across the entire genome and correlated with genetic, epigenetic, and transcriptional analyses. This review summarizes recent pan-genomic analyses of HIF binding and HIF-dependent transcriptional regulation.
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9

Kamikubo, Yasuhiko. "Genetic compensation of RUNX family transcription factors in leukemia". Cancer Science 109, nr 8 (sierpień 2018): 2358–63. http://dx.doi.org/10.1111/cas.13664.

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10

Ozanne, Bradford W., Heather J. Spence, Lynn C. McGarry i Robert F. Hennigan. "Invasion is a genetic program regulated by transcription factors". Current Opinion in Genetics & Development 16, nr 1 (luty 2006): 65–70. http://dx.doi.org/10.1016/j.gde.2005.12.012.

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11

Li, Zhonghai, Hye Ryun Woo i Hongwei Guo. "Genetic redundancy of senescence-associated transcription factors in Arabidopsis". Journal of Experimental Botany 69, nr 4 (22.12.2017): 811–23. http://dx.doi.org/10.1093/jxb/erx345.

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Mochdia, Keiichi, i Shun Tamaki. "Transcription Factor-Based Genetic Engineering in Microalgae". Plants 10, nr 8 (4.08.2021): 1602. http://dx.doi.org/10.3390/plants10081602.

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Sequence-specific DNA-binding transcription factors (TFs) are key components of gene regulatory networks. Advances in high-throughput sequencing have facilitated the rapid acquisition of whole genome assembly and TF repertoires in microalgal species. In this review, we summarize recent advances in gene discovery and functional analyses, especially for transcription factors in microalgal species. Specifically, we provide examples of the genome-scale identification of transcription factors in genome-sequenced microalgal species and showcase their application in the discovery of regulators involved in various cellular functions. Herein, we highlight TF-based genetic engineering as a promising framework for designing microalgal strains for microalgal-based bioproduction.
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13

Hontz, Robert D., Rachel O. Niederer, Joseph M. Johnson i Jeffrey S. Smith. "Genetic Identification of Factors That Modulate Ribosomal DNA Transcription inSaccharomyces cerevisiae". Genetics 182, nr 1 (6.03.2009): 105–19. http://dx.doi.org/10.1534/genetics.108.100313.

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14

Prochiantz, Alain, Julia Fuchs i Ariel A. Di Nardo. "Postnatal signalling with homeoprotein transcription factors". Philosophical Transactions of the Royal Society B: Biological Sciences 369, nr 1652 (26.09.2014): 20130518. http://dx.doi.org/10.1098/rstb.2013.0518.

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Homeoprotein (HP) transcription factors were originally identified for their embryonic cell-autonomous developmental functions. In this review, we discuss their postnatal and adult physiological functions based on the study of Otx2, Engrailed-1 and Engrailed-2 (collectively Engrailed). For Engrailed, we discuss its function in the cell-autonomous regulation of ventral midbrain dopaminergic neuron survival and physiology and in the non-cell-autonomous maintenance of axons. For Otx2, we describe how the protein is expressed in the choroid plexus and transported into cortical parvalbumin cells where it regulates plasticity in the visual cortex. These two examples illustrate how the understanding of HP postnatal and adult functions, including signalling functions, may lead to the identification of disease-associated genetic pathways and to the development of original therapeutic strategies.
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15

Tuteja, Renu, Abulaish Ansari i Virander Singh Chauhan. "Emerging Functions of Transcription Factors in Malaria Parasite". Journal of Biomedicine and Biotechnology 2011 (2011): 1–6. http://dx.doi.org/10.1155/2011/461979.

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Transcription is a process by which the genetic information stored in DNA is converted into mRNA by enzymes known as RNA polymerase. Bacteria use only one RNA polymerase to transcribe all of its genes while eukaryotes contain three RNA polymerases to transcribe the variety of eukaryotic genes. RNA polymerase also requires other factors/proteins to produce the transcript. These factors generally termed as transcription factors (TFs) are either associated directly with RNA polymerase or add in building the actual transcription apparatus. TFs are the most common tools that our cells use to control gene expression.Plasmodium falciparumis responsible for causing the most lethal form of malaria in humans. It shows most of its characteristics common to eukaryotic transcription but it is assumed that mechanisms of transcriptional control inP. falciparumsomehow differ from those of other eukaryotes. In this article we describe the studies on the main TFs such as myb protein, high mobility group protein and ApiA2 family proteins from malaria parasite. These studies show that these TFs are slowly emerging to have defined roles in the regulation of gene expression in the parasite.
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16

Ning, He, Su Yang, Baofang Fan, Cheng Zhu i Zhixiang Chen. "Expansion and Functional Diversification of TFIIB-Like Factors in Plants". International Journal of Molecular Sciences 22, nr 3 (23.01.2021): 1078. http://dx.doi.org/10.3390/ijms22031078.

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As sessile organisms, plants have evolved unique patterns of growth and development, elaborate metabolism and special perception and signaling mechanisms to environmental cues. Likewise, plants have complex and highly special programs for transcriptional control of gene expression. A case study for the special transcription control in plants is the expansion of general transcription factors, particularly the family of Transcription Factor IIB (TFIIB)-like factors with 15 members in Arabidopsis. For more than a decade, molecular and genetic analysis has revealed important functions of these TFIIB-like factors in specific biological processes including gametogenesis, pollen tube growth guidance, embryogenesis, endosperm development, and plant-microbe interactions. The redundant, specialized, and diversified roles of these TFIIB-like factors challenge the traditional definition of general transcription factors established in other eukaryotes. In this review, we discuss general transcription factors in plants with a focus on the expansion and functional analysis of plant TFIIB-like proteins to highlight unique aspects of plant transcription programs that can be highly valuable for understanding the molecular basis of plant growth, development and responses to stress conditions.
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17

Frank, Steven A. "Optimization of Transcription Factor Genetic Circuits". Biology 11, nr 9 (31.08.2022): 1294. http://dx.doi.org/10.3390/biology11091294.

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Transcription factors (TFs) affect the production of mRNAs. In essence, the TFs form a large computational network that controls many aspects of cellular function. This article introduces a computational method to optimize TF networks. The method extends recent advances in artificial neural network optimization. In a simple example, computational optimization discovers a four-dimensional TF network that maintains a circadian rhythm over many days, successfully buffering strong stochastic perturbations in molecular dynamics and entraining to an external day–night signal that randomly turns on and off at intervals of several days. This work highlights the similar challenges in understanding how computational TF and neural networks gain information and improve performance.
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18

Rothenberg, Ellen V. "Transcription factors specifically control change". Genes & Development 36, nr 21-24 (1.11.2022): 1097–99. http://dx.doi.org/10.1101/gad.350308.122.

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Transcription factors are defined by their sequence-specific binding to DNA and by their selective impacts on gene expression, depending on specific binding sites. The factor binding motifs in the DNA should thus represent a blueprint of regulatory logic, suggesting that transcription factor binding patterns on the genome (e.g., measured by ChIP-seq) should indicate which target genes the factors are directly controlling. However, although genetic data confirm high impacts of transcription factor perturbation in embryology, transcription factors bind to far more sites than the number of genes they dynamically regulate, when measured by direct perturbation in a given cell type. Also, deletion of carefully chosen transcription factor binding sites often gives disappointingly weak results. In a new study in the previous issue ofGenes & Development, Lo and colleagues (pp. 1079–1095) reconcile these contradictions by using an elegant experimental system to directly compare the roles of transcription factor–binding site interaction in gene regulation maintenance with roles of the same factor–site interactions in gene regulation through developmental change. They examine Oct4:Sox2 shared target genes under maintained versus reinduced pluripotency conditions within the same cell clone. The results show that the same factor–site interaction impacts can appear modest in assays in developmental steady-state but are far more important as regulatory catalysts of developmental change.
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Roksana, Zakharyan. "Transcription Factors in Schizophrenia: A Current View of Genetic Aspects". Scientific Journal of Genetics and Gene Therapy 2, nr 1 (30.12.2016): 017–21. http://dx.doi.org/10.17352/sjggt.000010.

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Damberg, M., H. Garpenstrand, J. Hallman i L. Oreland. "Genetic mechanisms of behavior—don't forget about the transcription factors". Molecular Psychiatry 6, nr 5 (29.08.2001): 503–10. http://dx.doi.org/10.1038/sj.mp.4000935.

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Pomposiello, Pablo J., i Bruce Demple. "Redox-operated genetic switches: the SoxR and OxyR transcription factors". Trends in Biotechnology 19, nr 3 (marzec 2001): 109–14. http://dx.doi.org/10.1016/s0167-7799(00)01542-0.

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Blancafort, P., E. I. Chen, B. Gonzalez, S. Bergquist, A. Zijlstra, D. Guthy, A. Brachat i in. "Genetic reprogramming of tumor cells by zinc finger transcription factors". Proceedings of the National Academy of Sciences 102, nr 33 (4.08.2005): 11716–21. http://dx.doi.org/10.1073/pnas.0501162102.

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Gerke, J., K. Lorenz i B. Cohen. "Genetic Interactions Between Transcription Factors Cause Natural Variation in Yeast". Science 323, nr 5913 (23.01.2009): 498–501. http://dx.doi.org/10.1126/science.1166426.

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Singh, Harinder. "Genetic analysis of transcription factors implicated in B lymphocyte development". Immunologic Research 13, nr 4 (grudzień 1994): 280–90. http://dx.doi.org/10.1007/bf02935619.

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Yu, Yaxin, Peter Eriksson i David J. Stillman. "Architectural Transcription Factors and the SAGA Complex Function in Parallel Pathways To Activate Transcription". Molecular and Cellular Biology 20, nr 7 (1.04.2000): 2350–57. http://dx.doi.org/10.1128/mcb.20.7.2350-2357.2000.

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ABSTRACT Recent work has shown that transcription of the yeastHO gene involves the sequential recruitment of a series of transcription factors. We have performed a functional analysis ofHO regulation by determining the ability of mutations inSIN1, SIN3, RPD3, andSIN4 negative regulators to permit HOexpression in the absence of certain activators. Mutations in theSIN1 (=SPT2) gene do not affect HOregulation, in contrast to results of other studies using anHO:lacZ reporter, and our data show that the regulatory properties of an HO:lacZ reporter differ from that of the native HO gene. Mutations in SIN3 andRPD3, which encode components of a histone deacetylase complex, show the same pattern of genetic suppression, and this suppression pattern differs from that seen in a sin4mutant. The Sin4 protein is present in two transcriptional regulatory complexes, the RNA polymerase II holoenzyme/mediator and the SAGA histone acetylase complex. Our genetic analysis allows us to conclude that Swi/Snf chromatin remodeling complex has multiple roles inHO activation, and the data suggest that the ability of the SBF transcription factor to bind to the HO promoter may be affected by the acetylation state of the HO promoter. We also demonstrate that the Nhp6 architectural transcription factor, encoded by the redundant NHP6A and NHP6B genes, is required for HO expression. Suppression analysis withsin3, rpd3, and sin4 mutations suggests that Nhp6 and Gcn5 have similar functions. A gcn5 nhp6a nhp6b triple mutant is extremely sick, suggesting that the SAGA complex and the Nhp6 architectural transcription factors function in parallel pathways to activate transcription. We find that disruption ofSIN4 allows this strain to grow at a reasonable rate, indicating a critical role for Sin4 in detecting structural changes in chromatin mediated by Gcn5 and Nhp6. These studies underscore the critical role of chromatin structure in regulating HO gene expression.
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26

Carpinelli, M. R., M. E. de Vries, S. M. Jane i S. Dworkin. "Grainyhead-like Transcription Factors in Craniofacial Development". Journal of Dental Research 96, nr 11 (11.07.2017): 1200–1209. http://dx.doi.org/10.1177/0022034517719264.

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Craniofacial development in vertebrates involves the coordinated growth, migration, and fusion of several facial prominences during embryogenesis, processes governed by strict genetic and molecular controls. A failure in any of the precise spatiotemporal sequences of events leading to prominence fusion often leads to anomalous facial, skull, and jaw formation—conditions termed craniofacial defects (CFDs). Affecting approximately 0.1% to 0.3% of live births, CFDs are a highly heterogeneous class of developmental anomalies, which are often underpinned by genetic mutations. Therefore, identifying novel disease-causing mutations in genes that regulate craniofacial development is a critical prerequisite to develop new preventive or therapeutic measures. The Grainyhead-like ( GRHL) transcription factors are one such gene family, performing evolutionarily conserved roles in craniofacial patterning. The antecedent member of this family, Drosophila grainyhead ( grh), is required for head skeleton development in fruit flies, loss or mutation of Grhl family members in mouse and zebrafish models leads to defects of both maxilla and mandible, and recently, mutations in human GRHL3 have been shown to cause or contribute to both syndromic (Van Der Woude syndrome) and nonsyndromic palatal clefts. In this review, we summarize the current knowledge regarding the craniofacial-specific function of the Grainyhead-like family in multiple model species, identify some of the major target genes regulated by the Grhl transcription factors in craniofacial patterning, and, by examining animal models, draw inferences as to how these data will inform the likely roles of GRHL factors in human CFDs comprising palatal clefting. By understanding the molecular networks regulated by Grhl2 and Grhl3 target genes in other systems, we can propose likely pathways that mediate the effects of these transcription factors in human palatogenesis.
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Gray, Paul A. "Transcription factors and the genetic organization of brain stem respiratory neurons". Journal of Applied Physiology 104, nr 5 (maj 2008): 1513–21. http://dx.doi.org/10.1152/japplphysiol.01383.2007.

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Breathing is a genetically determined behavior generated by neurons in the brain stem. Transcription factors, in part, determine the basic developmental identity of neurons, but the relationships between these genes and the neural populations generating and modulating respiration are unclear. The diversity of brain stem populations has been proposed to result from a combinatorial code of transcription factor expression corresponding to the anterior-posterior (A-P) and dorsal-ventral (D-V) location of a neuron's birth. I provide a schematic of transcription factor coding identifying at least 15 genetically distinct D-V subdivisions of brain stem neurons that, combined with A-P patterning, may provide a genetic organization of the brain stem in general, with the eventual goal of describing respiratory populations in particular. Using a combination of fate mapping in transgenic mouse lines and immunohistochemistry, we confirm the parabrachial nuclei are derived from a subset of Atoh1 expression progenitor neurons. I hypothesize the Kölliker-Fuse nucleus can be uniquely defined in the neonate mouse by the coexpression of the transcription factor FoxP2 in Atoh1-derived neurons of rhombomere 1.
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Augustin, Regina, Stefan F. Lichtenthaler, Michael Greeff, Jens Hansen, Wolfgang Wurst i Dietrich Trümbach. "Bioinformatics Identification of Modules of Transcription Factor Binding Sites in Alzheimer's Disease-Related Genes by In Silico Promoter Analysis and Microarrays". International Journal of Alzheimer's Disease 2011 (2011): 1–13. http://dx.doi.org/10.4061/2011/154325.

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The molecular mechanisms and genetic risk factors underlying Alzheimer's disease (AD) pathogenesis are only partly understood. To identify new factors, which may contribute to AD, different approaches are taken including proteomics, genetics, and functional genomics. Here, we used a bioinformatics approach and found that distinct AD-related genes share modules of transcription factor binding sites, suggesting a transcriptional coregulation. To detect additional coregulated genes, which may potentially contribute to AD, we established a new bioinformatics workflow with known multivariate methods like support vector machines, biclustering, and predicted transcription factor binding site modules by using in silico analysis and over 400 expression arrays from human and mouse. Two significant modules are composed of three transcription factor families: CTCF, SP1F, and EGRF/ZBPF, which are conserved between human and mouse APP promoter sequences. The specific combination of in silico promoter and multivariate analysis can identify regulation mechanisms of genes involved in multifactorial diseases.
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van Ouwerkerk, Antoinette F., Amelia W. Hall, Zachary A. Kadow, Sonja Lazarevic, Jasmeet S. Reyat, Nathan R. Tucker, Rangarajan D. Nadadur i in. "Epigenetic and Transcriptional Networks Underlying Atrial Fibrillation". Circulation Research 127, nr 1 (19.06.2020): 34–50. http://dx.doi.org/10.1161/circresaha.120.316574.

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Genome-wide association studies have uncovered over a 100 genetic loci associated with atrial fibrillation (AF), the most common arrhythmia. Many of the top AF-associated loci harbor key cardiac transcription factors, including PITX2, TBX5, PRRX1, and ZFHX3. Moreover, the vast majority of the AF-associated variants lie within noncoding regions of the genome where causal variants affect gene expression by altering the activity of transcription factors and the epigenetic state of chromatin. In this review, we discuss a transcriptional regulatory network model for AF defined by effector genes in Genome-wide association studies loci. We describe the current state of the field regarding the identification and function of AF-relevant gene regulatory networks, including variant regulatory elements, dose-sensitive transcription factor functionality, target genes, and epigenetic states. We illustrate how altered transcriptional networks may impact cardiomyocyte function and ionic currents that impact AF risk. Last, we identify the need for improved tools to identify and functionally test transcriptional components to define the links between genetic variation, epigenetic gene regulation, and atrial function.
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Chan, J. Y., X. L. Han i Y. W. Kan. "Cloning of Nrf1, an NF-E2-related transcription factor, by genetic selection in yeast". Proceedings of the National Academy of Sciences 90, nr 23 (1.12.1993): 11371–75. http://dx.doi.org/10.1073/pnas.90.23.11371.

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We have devised a complementation assay in yeast to clone mammalian transcriptional activators and have used it to identify a human basic leucine-zipper transcription factor that we have designated Nrf1 for NF-E2-related factor 1. Nrf1 potentially encodes a 742-aa protein and displays marked homology to the mouse and human NF-E2 transcription factors. Nrf1 activates transcription via NF-E2 binding sites in yeast cells. The ubiquitous expression pattern of Nrf1 and the range of promoters containing the NF-E2 binding motif suggest that this gene may play a role in the regulation of heme synthesis and ferritin genes.
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Byrne, M. E. "Shoot development – genetic interactions in the meristem". Biochemical Society Transactions 33, nr 6 (26.10.2005): 1499–501. http://dx.doi.org/10.1042/bst0331499.

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Development of the plant shoot is dependent on the shoot apical meristem. Interactions between KNOX homeodomain transcription factors and the myb domain transcription factor AS1 (ASYMMETRIC LEAVES1) regulate both meristem function as well as leaf patterning. This review summarizes these interactions.
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32

Shi, Hongyong, Xiaopeng Li, Minghui Lv i Jia Li. "BES1/BZR1 Family Transcription Factors Regulate Plant Development via Brassinosteroid-Dependent and Independent Pathways". International Journal of Molecular Sciences 23, nr 17 (5.09.2022): 10149. http://dx.doi.org/10.3390/ijms231710149.

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The BES1/BZR1 family is a plant-specific small group of transcription factors possessing a non-canonical bHLH domain. Genetic and biochemical analyses within the last two decades have demonstrated that members of this family are key transcription factors in regulating the expression of brassinosteroid (BR) response genes. Several recent genetic and evolutionary studies, however, have clearly indicated that the BES1/BZR1 family transcription factors also function in regulating several aspects of plant development via BR-independent pathways, suggesting they are not BR specific. In this review, we summarize our current understanding of this family of transcription factors, the mechanisms regulating their activities, DNA binding motifs, and target genes. We selectively discuss a number of their biological functions via BR-dependent and particularly independent pathways, which were recently revealed by loss-of-function genetic analyses. We also highlight a few possible future directions.
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David, Rajendran Host Antony, Stanislaus Antony Ceasar, Krishnaraj Thirugnanasambantham i Savarimuthu Ignacimuthu. "Genetic Engineering of Crop Plants for Drought Tolerance:Role of Transcription Factors". South Indian Journal of Biological Sciences 2, nr 2 (1.04.2016): 272. http://dx.doi.org/10.22205/sijbs/2016/v2/i2/100317.

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Robinson, Gertraud W., Keunsoo Kang, Kyung Hyun Yoo, Yong Tang, Bing-Mei Zhu, Daisuke Yamaji, Vera Colditz, Seung Jian Jang, Richard M. Gronostajski i Lothar Hennighausen. "Coregulation of Genetic Programs by the Transcription Factors NFIB and STAT5". Molecular Endocrinology 28, nr 5 (1.05.2014): 758–67. http://dx.doi.org/10.1210/me.2012-1387.

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35

Hoffmann, A. "Genetic analysis of NF- B/Rel transcription factors defines functional specificities". EMBO Journal 22, nr 20 (15.10.2003): 5530–39. http://dx.doi.org/10.1093/emboj/cdg534.

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Chen, Xuemei, Xin Jin, Ximei Li i Zhongxu Lin. "Genetic Mapping and Comparative Expression Analysis of Transcription Factors in Cotton". PLOS ONE 10, nr 5 (6.05.2015): e0126150. http://dx.doi.org/10.1371/journal.pone.0126150.

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37

Yu, Alice W., J. David Peery i Hyejung Won. "Limited Association between Schizophrenia Genetic Risk Factors and Transcriptomic Features". Genes 12, nr 7 (12.07.2021): 1062. http://dx.doi.org/10.3390/genes12071062.

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Schizophrenia is a polygenic disorder with many genomic regions contributing to schizophrenia risk. The majority of genetic variants associated with schizophrenia lie in the non-coding genome and are thought to contribute to transcriptional regulation. Extensive transcriptomic dysregulation has been detected from postmortem brain samples of schizophrenia-affected individuals. However, the relationship between schizophrenia genetic risk factors and transcriptomic features has yet to be explored. Herein, we examined whether varying gene expression features, including differentially expressed genes (DEGs), co-expression networks, and central hubness of genes, contribute to the heritability of schizophrenia. We leveraged quantitative trait loci and chromatin interaction profiles to identify schizophrenia risk variants assigned to the genes that represent different transcriptomic features. We then performed stratified linkage disequilibrium score regression analysis on these variants to estimate schizophrenia heritability enrichment for different gene expression features. Notably, DEGs and co-expression networks showed nominal heritability enrichment. This nominal association can be partly explained by cellular heterogeneity, as DEGs were associated with the genetic risk of schizophrenia in a cell type-specific manner. Moreover, DEGs were enriched for target genes of schizophrenia-associated transcription factors, suggesting that the transcriptomic signatures of schizophrenia are the result of transcriptional regulatory cascades elicited by genetic risk factors.
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38

Sommer, Hans, Wolfgang Nacken, Pio Beltran, Peter Huijser, Heike Pape, Rolf Hansen, Peter Flor, Heinz Saedler i Zsuzsanna Schwarz-Sommer. "Properties of deficiens, a homeotic gene involved in the control of flower morphogenesis in Antirrhinum majus". Development 113, Supplement_1 (1.01.1991): 169–75. http://dx.doi.org/10.1242/dev.113.supplement_1.169.

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deficiens, together with other homeotic genes, is involved in the genetic control of floral morphogenesis in A. majus. Mutations in this gene cause homeotic transformations of petals to sepals and stamens to carpels, thus producing male sterile flowers. The deduced DEF A protein shows homology to the DNA-binding domain of the transcription factors SRF of mammals (activating c-fos) and MCM1 of yeast (regulating mating type), suggesting that DEF A has a possible regulatory function as a transcription factor. Interestingly, DEF A belongs to a family of putative transcription factors, called the MADS box genes, whose DNA-binding domains show conserved homology. Two members of this family correlate with known morphogenetic mutants of Antirrhinum. DEF A is constantly expressed during flower development in all floral organs; it is strongly expressed in petals and stamens, but only at a low basal level in the other organs. Molecular, genetic and morphological observations with deficiens morphoalleles indicate that transcriptional and post-transcriptional control of deficiens specifies and diversifies its function in space and time.
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39

Kirchner, Jay, Steven L. Sanders, Edward Klebanow i P. Anthony Weil. "Molecular Genetic Dissection of TAF25, an Essential Yeast Gene Encoding a Subunit Shared by TFIID and SAGA Multiprotein Transcription Factors". Molecular and Cellular Biology 21, nr 19 (1.10.2001): 6668–80. http://dx.doi.org/10.1128/mcb.21.19.6668-6680.2001.

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ABSTRACT We have performed a systematic structure-function analysis of Saccharomyces cerevisiae TAF25, an evolutionarily conserved, single-copy essential gene which encodes the 206-amino-acid TAF25p protein. TAF25p is an integral subunit of both the 15-subunit general transcription factor TFIID and the multisubunit, chromatin-acetylating transcriptional coactivator SAGA. We used hydroxylamine mutagenesis, targeted deletion, alanine-scanning mutagenesis, high-copy suppression methods, and two-hybrid screening to dissect TAF25. Temperature-sensitive mutant strains generated were used for coimmunoprecipitation and transcription analyses to define the in vivo functions of TAF25p. The results of these analyses show that TAF25p is comprised of multiple mutable elements which contribute importantly to RNA polymerase II-mediated mRNA gene transcription.
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40

Hosoya, Tomonori, Mary Clifford, Régine Losson, Osamu Tanabe i James Douglas Engel. "TRIM28 is essential for erythroblast differentiation in the mouse". Blood 122, nr 23 (28.11.2013): 3798–807. http://dx.doi.org/10.1182/blood-2013-04-496166.

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Key Points Genetic loss of the transcriptional corepressor TRIM28 in adult mice results in deficient adult erythropoiesis in bone marrow, and anemia. TRIM28 controls the mRNA levels of multiple erythroid transcription factors, heme biosynthetic enzymes, and the apoptotic apparatus.
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41

Hayashi, Shunya, Mutsumi Watanabe, Makoto Kobayashi, Takayuki Tohge, Takashi Hashimoto i Tsubasa Shoji. "Genetic Manipulation of Transcriptional Regulators Alters Nicotine Biosynthesis in Tobacco". Plant and Cell Physiology 61, nr 6 (19.03.2020): 1041–53. http://dx.doi.org/10.1093/pcp/pcaa036.

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Abstract The toxic alkaloid nicotine is produced in the roots of Nicotiana species and primarily accumulates in leaves as a specialized metabolite. A series of metabolic and transport genes involved in the nicotine pathway are coordinately upregulated by a pair of jasmonate-responsive AP2/ERF-family transcription factors, NtERF189 and NtERF199, in the roots of Nicotiana tabacum (tobacco). In this study, we explored the potential of manipulating the expression of these transcriptional regulators to alter nicotine biosynthesis in tobacco. The transient overexpression of NtERF189 led to alkaloid production in the leaves of Nicotiana benthamiana and Nicotiana alata. This ectopic production was further enhanced by co-overexpressing a gene encoding a basic helix-loop-helix-family MYC2 transcription factor. Constitutive and leaf-specific overexpression of NtERF189 increased the accumulation of foliar alkaloids in transgenic tobacco plants but negatively affected plant growth. By contrast, in a knockout mutant of NtERF189 and NtERF199 obtained through CRISPR/Cas9-based genome editing, alkaloid levels were drastically reduced without causing major growth defects. Metabolite profiling revealed the impact of manipulating the nicotine pathway on a wide range of nitrogen- and carbon-containing metabolites. Our findings provide insights into the biotechnological applications of engineering metabolic pathways by targeting transcription factors.
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42

Lu, Hengwei, Yi-Ching Tang i Assaf Gottlieb. "Tissue-Specific Variations in Transcription Factors Elucidate Complex Immune System Regulation". Genes 13, nr 5 (23.05.2022): 929. http://dx.doi.org/10.3390/genes13050929.

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Gene expression plays a key role in health and disease. Estimating the genetic components underlying gene expression can thus help understand disease etiology. Polygenic models termed “transcriptome imputation” are used to estimate the genetic component of gene expression, but these models typically consider only the cis regions of the gene. However, these cis-based models miss large variability in expression for multiple genes. Transcription factors (TFs) that regulate gene expression are natural candidates for looking for additional sources of the missing variability. We developed a hypothesis-driven approach to identify second-tier regulation by variability in TFs. Our approach tested two models representing possible mechanisms by which variations in TFs can affect gene expression: variability in the expression of the TF and genetic variants within the TF that may affect the binding affinity of the TF to the TF-binding site. We tested our TF models in whole blood and skeletal muscle tissues and identified TF variability that can partially explain missing gene expression for 1035 genes, 76% of which explains more than the cis-based models. While the discovered regulation patterns were tissue-specific, they were both enriched for immune system functionality, elucidating complex regulation patterns. Our hypothesis-driven approach is useful for identifying tissue-specific genetic regulation patterns involving variations in TF expression or binding.
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43

Nakamichi, Norihito. "The Transcriptional Network in the Arabidopsis Circadian Clock System". Genes 11, nr 11 (29.10.2020): 1284. http://dx.doi.org/10.3390/genes11111284.

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The circadian clock is the biological timekeeping system that governs the approximately 24-h rhythms of genetic, metabolic, physiological and behavioral processes in most organisms. This oscillation allows organisms to anticipate and adapt to day–night changes in the environment. Molecular studies have indicated that a transcription–translation feedback loop (TTFL), consisting of transcriptional repressors and activators, is essential for clock function in Arabidopsis thaliana (Arabidopsis). Omics studies using next-generation sequencers have further revealed that transcription factors in the TTFL directly regulate key genes implicated in clock-output pathways. In this review, the target genes of the Arabidopsis clock-associated transcription factors are summarized. The Arabidopsis clock transcriptional network is partly conserved among angiosperms. In addition, the clock-dependent transcriptional network structure is discussed in the context of plant behaviors for adapting to day–night cycles.
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44

Do, Eunsoo, Yong-Joon Cho, Donghyeun Kim, James W. Kronstad i Won Hee Jung. "A Transcriptional Regulatory Map of Iron Homeostasis Reveals a New Control Circuit for Capsule Formation in Cryptococcus neoformans". Genetics 215, nr 4 (24.06.2020): 1171–89. http://dx.doi.org/10.1534/genetics.120.303270.

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Iron is essential for the growth of the human fungal pathogen Cryptococcus neoformans within the vertebrate host, and iron sensing contributes to the elaboration of key virulence factors, including the formation of the polysaccharide capsule. C. neoformans employs sophisticated iron acquisition and utilization systems governed by the transcription factors Cir1 and HapX. However, the details of the transcriptional regulatory networks that are governed by these transcription factors and connections to virulence remain to be defined. Here, we used chromatin immunoprecipitation followed by next-generation sequencing (ChIP-seq) and transcriptome analysis (RNA-seq) to identify genes directly regulated by Cir1 and/or HapX in response to iron availability. Overall, 40 and 100 genes were directly regulated by Cir1, and 171 and 12 genes were directly regulated by HapX, under iron-limited and replete conditions, respectively. More specifically, we found that Cir1 directly controls the expression of genes required for iron acquisition and metabolism, and indirectly governs capsule formation by regulating specific protein kinases, a regulatory connection not previously revealed. HapX regulates the genes responsible for iron-dependent pathways, particularly under iron-depleted conditions. By analyzing target genes directly bound by Cir1 and HapX, we predicted the binding motifs for the transcription factors and verified that the purified proteins bind these motifs in vitro. Furthermore, several direct target genes were coordinately and reciprocally regulated by Cir1 and HapX, suggesting that these transcription factors play conserved roles in the response to iron availability. In addition, biochemical analyses revealed that Cir1 and HapX are iron-containing proteins, implying that the regulatory networks of Cir1 and HapX may be influenced by the incorporation of iron into these proteins. Taken together, our identification of the genome-wide transcriptional networks provides a detailed understanding of the iron-related regulatory landscape, establishes a new connection between Cir1 and kinases that regulate capsule, and underpins genetic and biochemical analyses that reveal iron-sensing mechanisms for Cir1 and HapX in C. neoformans.
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45

Zhu, Qian, Xavier Tekpli, Olga G. Troyanskaya i Vessela N. Kristensen. "Subtype-specific transcriptional regulators in breast tumors subjected to genetic and epigenetic alterations". Bioinformatics 36, nr 4 (16.09.2019): 994–99. http://dx.doi.org/10.1093/bioinformatics/btz709.

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Abstract Motivation Breast cancer consists of multiple distinct tumor subtypes, and results from epigenetic and genetic aberrations that give rise to distinct transcriptional profiles. Despite previous efforts to understand transcriptional deregulation through transcription factor networks, the transcriptional mechanisms leading to subtypes of the disease remain poorly understood. Results We used a sophisticated computational search of thousands of expression datasets to define extended signatures of distinct breast cancer subtypes. Using ENCODE ChIP-seq data of surrogate cell lines and motif analysis we observed that these subtypes are determined by a distinct repertoire of lineage-specific transcription factors. Furthermore, specific pattern and abundance of copy number and DNA methylation changes at these TFs and targets, compared to other genes and to normal cells were observed. Overall, distinct transcriptional profiles are linked to genetic and epigenetic alterations at lineage-specific transcriptional regulators in breast cancer subtypes. Availability and implementation The analysis code and data are deposited at https://bitbucket.org/qzhu/breast.cancer.tf/. Supplementary information Supplementary data are available at Bioinformatics online.
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46

Bilecki, Wiktor, i Marzena Maćkowiak. "Gene Expression and Epigenetic Regulation in the Prefrontal Cortex of Schizophrenia". Genes 14, nr 2 (18.01.2023): 243. http://dx.doi.org/10.3390/genes14020243.

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Schizophrenia pathogenesis remains challenging to define; however, there is strong evidence that the interaction of genetic and environmental factors causes the disorder. This paper focuses on transcriptional abnormalities in the prefrontal cortex (PFC), a key anatomical structure that determines functional outcomes in schizophrenia. This review summarises genetic and epigenetic data from human studies to understand the etiological and clinical heterogeneity of schizophrenia. Gene expression studies using microarray and sequencing technologies reported the aberrant transcription of numerous genes in the PFC in patients with schizophrenia. Altered gene expression in schizophrenia is related to several biological pathways and networks (synaptic function, neurotransmission, signalling, myelination, immune/inflammatory mechanisms, energy production and response to oxidative stress). Studies investigating mechanisms driving these transcriptional abnormalities focused on alternations in transcription factors, gene promoter elements, DNA methylation, posttranslational histone modifications or posttranscriptional regulation of gene expression mediated by non-coding RNAs.
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47

Cox, James Shell, i Michael W. Van Dyke. "General and Genomic DNA-Binding Specificity for the Thermus thermophilus HB8 Transcription Factor TTHB023". Biomolecules 10, nr 1 (6.01.2020): 94. http://dx.doi.org/10.3390/biom10010094.

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Transcription factors are proteins that recognize specific DNA sequences and affect local transcriptional processes. They are the primary means by which all organisms control specific gene expression. Understanding which DNA sequences a particular transcription factor recognizes provides important clues into the set of genes that they regulate and, through this, their potential biological functions. Insights may be gained through homology searches and genetic means. However, these approaches can be misleading, especially when comparing distantly related organisms or in cases of complicated transcriptional regulation. In this work, we used a biochemistry-based approach to determine the spectrum of DNA sequences specifically bound by the Thermus thermophilus HB8 TetR-family transcription factor TTHB023. The consensus sequence 5′–(a/c)Y(g/t)A(A/C)YGryCR(g/t)T(c/a)R(g/t)–3′ was found to have a nanomolar binding affinity with TTHB023. Analyzing the T. thermophilus HB8 genome, several TTHB023 consensus binding sites were mapped to the promoters of genes involved in fatty acid biosynthesis. Notably, some of these were not identified previously through genetic approaches, ostensibly given their potential co-regulation by the Thermus thermophilus HB8 TetR-family transcriptional repressor TTHA0167. Our investigation provides additional evidence supporting the usefulness of a biochemistry-based approach for characterizing putative transcription factors, especially in the case of cooperative regulation.
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48

Babbar, N., i E. W. Gerner. "Polyamines as modifiers of genetic risk factors in human intestinal cancers". Biochemical Society Transactions 31, nr 2 (1.04.2003): 388–92. http://dx.doi.org/10.1042/bst0310388.

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Polyamines are downstream mediators of genetic risk factors in human intestinal cancers. The adenomatous polyposis coli (APC) tumour-suppressor gene, which is mutated in essentially all human colon cancers, regulates the expression of several e-box transcription factors. These factors, in turn, regulate the transcription of ornithine decarboxylase (ODC), the first enzyme in polyamine synthesis. The Kirsten ras (K-ras) oncogene regulates the expression of several genes, including suppressing the expression of peroxisomal proliferator-activated receptor γ (PPARγ). This PPAR, in turn, activates the expression of the spermidine/spermine-N1-acetyltransferase (SSAT), the first enzyme in polyamine catabolism. The non-steroidal anti-inflammatory drug (NSAID) sulindac induces the transcription of SSAT via activation of PPARγ. Inactivation of the APC tumour-suppressor gene, and the activation of K-ras, have a combined effect on increasing tissue polyamine contents due to increased synthesis and decreased catabolism of the polyamines. Pharmacological strategies for suppressing ODC (e.g. the enzyme-activated inhibitor α-difluoromethylornithine) and activating SSAT (e.g. NSAIDs) are potent inhibitors of intestinal carcinogenesis in rodent models. Clinical trials combining these classes of agent in humans with risk factors for colon cancer are in progress.
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49

Zhang, Dawn X., i Christopher K. Glass. "Towards an understanding of cell-specific functions of signal-dependent transcription factors". Journal of Molecular Endocrinology 51, nr 3 (15.10.2013): T37—T50. http://dx.doi.org/10.1530/jme-13-0216.

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The ability to regulate gene expression in a cell-specific manner is a feature of many broadly expressed signal-dependent transcription factors (SDTFs), including nuclear hormone receptors and transcription factors that are activated by cell surface receptors for extracellular signals. As the most plastic cells of the hematopoietic system, macrophages are responsive to a wide spectrum of regulatory molecules and provide a robust model system for investigation of the basis for cell-specific transcriptional responses at a genome-wide level. Here, focusing on recent studies in macrophages, we review the evidence suggesting a model in which cell-specific actions of SDTFs are the consequence of priming functions of lineage determining transcription factors. We also discuss recent findings relating lineage-determining and SDTF activity to alterations in the epigenetic landscape as well as the production and function of enhancer RNAs. These findings have implications for the understanding of how natural genetic variation impacts cell-specific programs of gene expression and suggest new approaches for altering gene expressionin vivo.
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50

Xu, Jun, Jenny Chong i Dong Wang. "Opposite roles of transcription elongation factors Spt4/5 and Elf1 in RNA polymerase II transcription through B-form versus non-B DNA structures". Nucleic Acids Research 49, nr 9 (20.04.2021): 4944–53. http://dx.doi.org/10.1093/nar/gkab240.

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Abstract Transcription elongation can be affected by numerous types of obstacles, such as nucleosome, pausing sequences, DNA lesions and non-B-form DNA structures. Spt4/5 and Elf1 are conserved transcription elongation factors that promote RNA polymerase II (Pol II) bypass of nucleosome and pausing sequences. Importantly, genetic studies have shown that Spt4/5 plays essential roles in the transcription of expanded nucleotide repeat genes associated with inherited neurological diseases. Here, we investigate the function of Spt4/5 and Elf1 in the transcription elongation of CTG•CAG repeat using an in vitro reconstituted yeast transcription system. We found that Spt4/5 helps Pol II transcribe through the CTG•CAG tract duplex DNA, which is in good agreement with its canonical roles in stimulating transcription elongation. In sharp contrast, surprisingly, we revealed that Spt4/5 greatly inhibits Pol II transcriptional bypass of CTG and CAG slip-out structures. Furthermore, we demonstrated that transcription elongation factor Elf1 individually and cooperatively with Spt4/5 inhibits Pol II bypass of the slip-out structures. This study uncovers the important functional interplays between template DNA structures and the function of transcription elongation factors. This study also expands our understanding of the functions of Spt4/5 and Elf1 in transcriptional processing of trinucleotide repeat DNA.
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