Relevant bibliographies by topics / Epigenetics: histone deacetylase

Academic literature on the topic 'Epigenetics: histone deacetylase'

Author: Grafiati
Published: 9 March 2023
Last updated: 10 March 2023

Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles

Select a source type:

Contents

Consult the lists of relevant articles, books, theses, conference reports, and other scholarly sources on the topic 'Epigenetics: histone deacetylase.'

Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.

You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.

Journal articles on the topic "Epigenetics: histone deacetylase"

1

Ružić, Dušan, Nemanja Đoković, Katarina Nikolić, and Zorica Vujić. "Medicinal chemistry of histone deacetylase inhibitors." Arhiv za farmaciju 71, no. 2 (2021): 73–100. http://dx.doi.org/10.5937/arhfarm71-30618.

Full text
Abstract:
Today, we are witnessing an explosion of scientific concepts in cancer chemotherapy. It has been considered for a long time that genetic instability in cancer should be treated with drugs that directly damage the DNA. Understanding the molecular basis of malignant diseases shed light on studying phenotypic plasticity. In the era of epigenetics, many efforts are being made to alter the aberrant homeostasis in cancer without modifying the DNA sequence. One such strategy is modulation of the lysine acetylome in human cancers. To remove the acetyl group from the histones, cells use the enzymes that are called histone deacetylases (HDACs). The disturbed equilibrium between acetylation and deacetylation on lysine residues of histones can be manipulated with histone deacetylase inhibitors (HDACi). Throughout the review, an effort will be made to present the mechanistic basis of targeting the HDAC isoforms, discovered selective HDAC inhibitors, and their therapeutical implications and expectations in modern drug discovery.
APA, Harvard, Vancouver, ISO, and other styles
2

Licciardi, Paul V., and Tom C. Karagiannis. "Regulation of Immune Responses by Histone Deacetylase Inhibitors." ISRN Hematology 2012 (March 18, 2012): 1–10. http://dx.doi.org/10.5402/2012/690901.

Full text
Abstract:
Both genetic and epigenetic factors are important regulators of the immune system. There is an increasing body of evidence attesting to epigenetic modifications that influence the development of distinct innate and adaptive immune response cells. Chromatin remodelling via acetylation, methylation, phosphorylation, and ubiquitination of histone proteins as well as DNA, methylation is epigenetic mechanisms by which immune gene expression can be controlled. In this paper, we will discuss the role of epigenetics in the regulation of host immunity, with particular emphasis on histone deacetylase inhibitors. In particular, the role of HDAC inhibitors as a new class of immunomodulatory therapeutics will also be reviewed.
APA, Harvard, Vancouver, ISO, and other styles
3

Ikeda, Yuka, Nozomi Nagase, Ai Tsuji, Kurumi Taniguchi, Yasuko Kitagishi, and Satoru Matsuda. "Comprehension of the Relationship between Autophagy and Reactive Oxygen Species for Superior Cancer Therapy with Histone Deacetylase Inhibitors." Oxygen 1, no. 1 (July 25, 2021): 22–31. http://dx.doi.org/10.3390/oxygen1010004.

Full text
Abstract:
Epigenetics contains various mechanisms by which cells employ to regulate the transcription of many DNAs. Histone acetylation is an obvious example of the epigenetic mechanism regulating the expression of several genes by changing chromatin accessibility. Histone deacetylases (HDACs) are a class of enzymes that play a critical role in the epigenetic regulation by deacetylation of histone proteins. Inhibitors of the histone deacetylase could result in hyperacetylation of histones, which eventually induce various cellular consequences such as generation of reactive oxygen species (ROS), activation of apoptotic pathways, and initiating autophagy. In particular, excessive levels of ROS have been proposed to contribute to the pathophysiology of various diseases including cancer. Cancers are, as it were, a class of redox diseases. Low levels of ROS are beneficial for cells, however, cancer cells generally have high levels of ROS, which makes them more susceptible than normal cells to the further increases of ROS levels. Cancer cells exhibit metabolic alterations for managing to sustain these oxidative stresses. There is a growing interest in the use of HDAC inhibitors as promising cancer therapeutics with potentiating the activity of established therapeutic applications. Therefore, it should be important to understand the underlying relationship between the regulation of HDACs, ROS production, and cancer cell biology.
APA, Harvard, Vancouver, ISO, and other styles
4

Hassell. "Histone Deacetylases and their Inhibitors in Cancer Epigenetics." Diseases 7, no. 4 (November 1, 2019): 57. http://dx.doi.org/10.3390/diseases7040057.

Full text
Abstract:
Histone deacetylases (HDAC) and histone deacetylase inhibitors (HDACi) have greatly impacted the war on cancer. Their role in epigenetics has significantly altered the development of anticancer drugs used to treat the most rare, persistent forms of cancer. During transcription, HDAC and HDACi are used to regulate the genetic mutations found in cancerous cells by removing and/or preventing the removal of the acetyl group on specific histones. This activity determines the relaxed or condensed conformation of the nucleosome, changing the accessibility zones for transcription factors. These modifications lead to other biological processes for the cell, including cell cycle progression, proliferation, and differentiation. Each HDAC and HDACi class or group has a distinctive mechanism of action that can be utilized to halt the progression of cancerous cell growth. While the use of HDAC- and HDACi-derived compounds are relatively new in treatment of cancers, they have a proven efficacy when the appropriately utilized. This following manuscript highlights the mechanisms of action utilized by HDAC and HDACi in various cancer, their role in epigenetics, current drug manufacturers, and the impact predicative modeling systems have on cancer therapeutic drug discovery.
APA, Harvard, Vancouver, ISO, and other styles
5

Peng, Xiaopeng, Guochao Liao, Pinghua Sun, Zhiqiang Yu, and Jianjun Chen. "An Overview of HDAC Inhibitors and their Synthetic Routes." Current Topics in Medicinal Chemistry 19, no. 12 (July 30, 2019): 1005–40. http://dx.doi.org/10.2174/1568026619666190227221507.

Full text
Abstract:
Epigenetics play a key role in the origin, development and metastasis of cancer. Epigenetic processes include DNA methylation, histone acetylation, histone methylation, and histone phosphorylation, among which, histone acetylation is the most common one that plays important roles in the regulation of normal cellular processes, and is controlled by histone deacetylases (HDACs) and histone acetyltransferases (HATs). HDACs are involved in the regulation of many key cellular processes, such as DNA damage repair, cell cycle control, autophagy, metabolism, senescence and chaperone function, and can lead to oncogene activation. As a result, HDACs are considered to be an excellent target for anti-cancer therapeutics like histone deacetylase inhibitors (HDACi) which have attracted much attention in the last decade. A wide-ranging knowledge of the role of HDACs in tumorigenesis, and of the action of HDACi, has been achieved. The primary purpose of this paper is to summarize recent HDAC inhibitors and the synthetic routes as well as to discuss the direction for the future development of new HDAC inhibitors.
APA, Harvard, Vancouver, ISO, and other styles
6

Drożak, Paulina, Łukasz Bryliński, and Joanna Zawitkowska. "A Comprehensive Overview of Recent Advances in Epigenetics in Pediatric Acute Lymphoblastic Leukemia." Cancers 14, no. 21 (November 1, 2022): 5384. http://dx.doi.org/10.3390/cancers14215384.

Full text
Abstract:
Recent years have brought a novel insight into our understanding of childhood acute lymphoblastic leukemia (ALL), along with several breakthrough treatment methods. However, multiple aspects of mechanisms behind this disease remain to be elucidated. Evidence suggests that leukemogenesis in ALL is widely influenced by epigenetic modifications. These changes include: DNA hypermethylation, histone modification and miRNA alteration. DNA hypermethylation in promoter regions, which leads to silencing of tumor suppressor genes, is a common epigenetic alteration in ALL. Histone modifications are mainly caused by an increased expression of histone deacetylases. A dysregulation of miRNA results in changes in the expression of their target genes. To date, several hundred genes were identified as suppressed by epigenetic mechanisms in ALL. What is promising is that epigenetic alterations in ALL may be used as potential biomarkers for classification of subtypes, predicting relapse and disease progression and assessing minimal residual disease. Furthermore, since epigenetic lesions are potentially reversible, an activation of epigenetically silenced genes with the use of hypomethylating agents or histone deacetylase inhibitors may be utilized as a therapeutic strategy for ALL. The following review summarizes our current knowledge about epigenetic modifications in ALL and describes potential uses of epigenetics in the clinical management of this disease.
APA, Harvard, Vancouver, ISO, and other styles
7

Amarante, Anderson de Mendonça, Isabel Caetano de Abreu da Silva, Vitor Coutinho Carneiro, Amanda Roberta Revoredo Vicentino, Marcia de Amorim Pinto, Luiza Mendonça Higa, Kanhu Charan Moharana, et al. "Zika virus infection drives epigenetic modulation of immunity by the histone acetyltransferase CBP of Aedes aegypti." PLOS Neglected Tropical Diseases 16, no. 6 (June 27, 2022): e0010559. http://dx.doi.org/10.1371/journal.pntd.0010559.

Full text
Abstract:
Epigenetic mechanisms are responsible for a wide range of biological phenomena in insects, controlling embryonic development, growth, aging and nutrition. Despite this, the role of epigenetics in shaping insect-pathogen interactions has received little attention. Gene expression in eukaryotes is regulated by histone acetylation/deacetylation, an epigenetic process mediated by histone acetyltransferases (HATs) and histone deacetylases (HDACs). In this study, we explored the role of the Aedes aegypti histone acetyltransferase CBP (AaCBP) after infection with Zika virus (ZIKV), focusing on the two main immune tissues, the midgut and fat body. We showed that the expression and activity of AaCBP could be positively modulated by blood meal and ZIKV infection. Nevertheless, Zika-infected mosquitoes that were silenced for AaCBP revealed a significant reduction in the acetylation of H3K27 (CBP target marker), followed by downmodulation of the expression of immune genes, higher titers of ZIKV and lower survival rates. Importantly, in Zika-infected mosquitoes that were treated with sodium butyrate, a histone deacetylase inhibitor, their capacity to fight virus infection was rescued. Our data point to a direct correlation among histone hyperacetylation by AaCBP, upregulation of antimicrobial peptide genes and increased survival of Zika-infected-A. aegypti.
APA, Harvard, Vancouver, ISO, and other styles
8

Santana, Dalileia Aparecida, Marilia de Arruda Cardoso Smith, and Elizabeth Suchi Chen. "Histone Modifications in Alzheimer’s Disease." Genes 14, no. 2 (January 29, 2023): 347. http://dx.doi.org/10.3390/genes14020347.

Full text
Abstract:
Since Late-onset Alzheimer’s disease (LOAD) derives from a combination of genetic variants and environmental factors, epigenetic modifications have been predicted to play a role in the etiopathology of LOAD. Along with DNA methylation, histone modifications have been proposed as the main epigenetic modifications that contribute to the pathologic mechanisms of LOAD; however, little is known about how these mechanisms contribute to the disease’s onset or progression. In this review, we highlighted the main histone modifications and their functional role, including histone acetylation, histone methylation, and histone phosphorylation, as well as changes in such histone modifications that occur in the aging process and mainly in Alzheimer’s disease (AD). Furthermore, we pointed out the main epigenetic drugs tested for AD treatment, such as those based on histone deacetylase (HDAC) inhibitors. Finally, we remarked on the perspectives around the use of such epigenetics drugs for treating AD.
APA, Harvard, Vancouver, ISO, and other styles
9

Saco, Tara V., Prasanna Tamarapu Parthasarathy, Young Cho, Richard F. Lockey, and Narasaiah Kolliputi. "Role of epigenetics in pulmonary hypertension." American Journal of Physiology-Cell Physiology 306, no. 12 (June 15, 2014): C1101—C1105. http://dx.doi.org/10.1152/ajpcell.00314.2013.

Full text
Abstract:
A significant amount of research has been conducted to examine the pathologic processes and epigenetic mechanisms contributing to peripheral hypertension. However, few studies have been carried out to understand the vascular remodeling behind pulmonary hypertension (PH), including peripheral artery muscularization, medial hypertrophy and neointima formation in proximal arteries, and plexiform lesion formation. Similarly, research examining some of the epigenetic principles that may contribute to this vascular remodeling, such as DNA methylation and histone modification, is minimal. The understanding of these principles may be the key to developing new and more effective treatments for PH. The purpose of this review is to summarize epigenetic research conducted in the field of hypertension that could possibly be used to understand the epigenetics of PH. Possible future therapies that could be pursued using information from these studies include selective histone deacetylase inhibitors and targeted DNA methyltransferases. Both of these could potentially be used to silence proproliferative or antiapoptotic genes that lead to decreased smooth muscle cell proliferation. Epigenetics may provide a glimmer of hope for the eventual improved treatment of this highly morbid and debilitating disease.
APA, Harvard, Vancouver, ISO, and other styles
10

Stintzing, Sebastian, Ralf Kemmerling, Tobias Kiesslich, Beate Alinger, Matthias Ocker, and Daniel Neureiter. "Myelodysplastic Syndrome and Histone Deacetylase Inhibitors: “To Be or Not to Be Acetylated”?" Journal of Biomedicine and Biotechnology 2011 (2011): 1–15. http://dx.doi.org/10.1155/2011/214143.

Full text
Abstract:
Myelodysplastic syndrome (MDS) represents a heterogeneous group of diseases with clonal proliferation, bone marrow failure and increasing risk of transformation into an acute myeloid leukaemia. Structured guidelines are developed for selective therapy based on prognostic subgroups, age, and performance status. Although many driving forces of disease phenotype and biology are described, the complete and possibly interacting pathogenetic pathways still remain unclear. Epigenetic investigations of cancer and haematologic diseases like MDS give new insights into the pathogenesis of this complex disease. Modifications of DNA or histones via methylation or acetylation lead to gene silencing and altered physiology relevant for MDS. First clinical trials give evidence that patients with MDS could benefit from epigenetic treatment with, for example, DNA methyl transferase inhibitors (DNMTi) or histone deacetylase inhibitors (HDACi). Nevertheless, many issues of HDACi remain incompletely understood and pose clinical and translational challenges. In this paper, major aspects of MDS, MDS-associated epigenetics and the potential use of HDACi are discussed.
APA, Harvard, Vancouver, ISO, and other styles
More sources

Dissertations / Theses on the topic "Epigenetics: histone deacetylase"

1

Tian, Lu. "Arabidopsis thaliana histone deacetylase 1 (AtHD1) and epigenetic regulation." Diss., Texas A&M University, 2003. http://hdl.handle.net/1969.1/23.

Full text
Abstract:
Epigenetic regulation is a mechanism by which heritable changes in gene expression are controlled by chromatin status rather than primary DNA sequence. Changes in chromatin structure affect accessibility of DNA elements to the transcriptional machinery and thus affect transcription activity of the gene. A key event in this process is reversible modification of core histones, which is catalyzed by histone acetyltransferases (HATs) and histone deacetylases (HDs, HDAs, or HDACs). In general, histone deacetylation is related to transcriptional gene silencing, whereas acetylation is associated with gene activation.To study the role of histone deacetylase in plant gene regulation and development, we generated constitutive antisense histone deacetylase 1 (CASH) transgenic plants. AtHD1 is a homolog of RPD3 protein, a global transcriptional regulator in yeast. Expression of the antisense AtHD1 caused dramatic reduction in endogenous AtHD1 transcription, resulting in accumulation of acetylated histones. Down-regulation of histone deacetylation caused a variety of growth and developmental abnormalities and ectopic expression of tissue-specific genes. However, changes in genomic DNA methylation were not detected in repetitive DNA sequences in the transgenic plants.We also identified a T-DNA insertion line in exon 2 of AtHD1 gene (athd1-t1), resulting in a null allele at the locus. The complete inhibition of the AtHD1 expression induced growth and developmental defects similar to those of CASH transgenic plants. The phenotypic abnormalities were heritable across the generations in the mutants. When the athd1-t1/athd1-t1 plants were crossed to wild-type plants, the mutant phenotype was corrected in the F1 hybrids, which correlated with the AtHD1 expression and reduction of histone H4 Lys12 acetylation. Microarray analysis was applied to determine genome-wide changes in transcriptional profiles in the athd1-t1 mutant. Approximately 6.7% (1,753) of the genes were differentially expressed in leaves between the wild-type (Ws) and the athd1-t1 mutant, whereas 4.8% (1,263) of the genes were up- or down-regulated in flower buds of the mutant. These affected genes were randomly distributed across five chromosomes of Arabidopsis and represented a wide range of biological functions. Chromatin immunoprecipitation assays indicated that the activation for a subset of genes was directly associated with changes in acetylation profiles.
APA, Harvard, Vancouver, ISO, and other styles
2

Petrone, Anna Maria. "Functional Characterization of Candida albicans Hst3p histone deacetylase." Doctoral thesis, Universita degli studi di Salerno, 2019. http://elea.unisa.it:8080/xmlui/handle/10556/4269.

Full text
Abstract:
2017 - 2018
The unicellular eukaryotic organism Candida albicans is one of the most important fungi in medicine, used as experimental model to study fungal pathologies and the underlying biology of dimorphic fungi. This fungus is a component of the human mucosal microbiota; it is normally found as a commensal in vaginal and oral mucosal districts, and in the gastrointestinal tract. However, at these sites it behaves as an opportunistic pathogen: following environmental changes in the host this fungus can become pathogenic, leading to invasive and lethal infections in susceptible individuals. Therefore, during the last decades, Candida has emerged as a major human fungal pathogen responsible for an extended variety of mucosal and systemic infections. The ability of this opportunistic fungus to cause and propagate successfully infections is linked to the expression of different and alternative virulence factors. Its key virulence trait is its morphological plasticity: its ability to shift from oval budding yeasts to elongated cell structures (pseudohyphal and hyphal filaments) responding to diverse and numerous environmental cues. Adaptive chromatin changes promote Candida variability and phenotypic plasticity. Therefore, epigenetic regulation of gene expression is considerably involved in the morphogenesis and virulence of this polymorphic fungus. Adaptation of C. albicans to drug pressure, yeast to hyphae transition, biofilm formation, white-opaque switch are important pathogenic mechanisms, in which posttranslational histone modifications play a prominent role. In particular, acetylation – deacetylation of histones modulates morphological switch in C. albicans and, consequently, this modification is correlated to fungal virulence. Histone H3 Lys56 acetylation (H3K56ac) is an important post-translational modification in yeast, that contributes to fungal genome stability. In C. albicans, acetylation levels of H3K56 are regulated by two enzymes with fungal-specific properties: the acetyl transferase Rtt109p and the NAD+-dependent histone deacetylase (sirtuin) Hst3p, encoded, respectively, by RTT109 and HST3 genes. HST3 is an essential gene for C. albicans: homozygous deletion mutants for this sequence are not viable. The essentiality of HST3 gene for C. albicans viability, combined with fungal-specific properties of its enzyme Hst3p, make it an attractive potential target for antifungal therapy. Focus of this study was to examine the molecular pathways regulated by Hst3p of C. albicans. Considering that deletion of this sirtuin is lethal for this fungus, it is intuitive to understand that it regulates vital process in the fungal cell. As histone deacetylase, Hst3p modulates gene expression, in particular induces the repressive state of chromatin, inhibiting transcriptional activation. Consequently, deletion of this gene or repression of its protein induces dysregulation of gene expression, leading to fungal death. Based on these considerations I focused my interest on this fungal protein, in order to characterize its role in C. albicans biology and virulence and its downstream targets, as potential new targets for the treatment of fungal infections. Substrate of Hst3p is the acetylated histone H3 Lysine 56. To analyse the effect of Hst3p inhibition on its substrate, I grew up C. albicans in the presence of nicotinamide (NAM), a non-specific sirtuin-inhibitor. Mass spectrometry analysis allowed me to evaluate, for the first time, acetylation levels of H3K56 during Candida growth and their variations upon NAM treatment. Interestingly, nicotinamide treatment induced the accumulation of H3K56 acetylation levels during C. albicans growth, demonstrating the inhibitory effect of NAM on Hst3p activity. One important attribute of Candida is its morphological variability, which is the result of the adaptive response to environmental changes which in turn this morphological plasticity triggers infection. To study the role of Hst3p in fungal virulence, I analyzed the potential involvement of this sirtuin in phenotypic switch. Morphological analyses were performed under NAM treatment to investigate the effect of Hst3p inhibition on cell duplication and filamentation. Hst3p inhibition resulted in a reduction of fungal growth rate and alteration of yeast-hyphae transition in C. albicans: NAM induced an abnormal filamentous growth, with formation of V-shaped hyphae under conditions that normally maintain the yeast shape of Candida. This phenotypic analysis was performed also on two azole-resistant strains of C. albicans to investigate the role of Hst3p in drug resistance. Hst3p inhibition had similar effect on the resistance strains compared to the control wild-type strain, inducing morphological alterations and reducing cell duplication rate. These phenotypic assays highlighted the effect of Hst3p inhibition on regulation of Candida morphology. V-shaped hyphae formation in Candida in non-inducing filamentation conditions require the structural rearrangement of the whole cell, which is a result of alteration in gene expression, induced by NAM treatment. Based on these considerations, I analysed the entire transcriptome of C. albicans strain SC5314 by RNA-sequencing to investigate whether the inhibition of Hst3p by NAM was responsible for changes in the pattern of expression of Virulence-related Genes. This analysis showed that gene categories most dysregulated upon NAM treatment are those associated with hyphal growth, adherence, white-opaque switch, drug resistance and cell wall maintenance. RNA-Sequencing analysis allowed to identify some dysregulated genes upon Hst3p inhibition; considering that no alteration in gene expression was detected for up-stream members of pathways that control these dysregulated genes, to verify if the expression of these genes is regulated epigenetically by H3K56 acetylation, future experiments of chromatin immunoprecipitation (ChIP) will be performed. To select inhibitors of Hst3p to be used as potential fungicidal compounds, I expressed and purified both the full length and a short sequence of recombinant Hst3p. These proteins did not show enzymatic activity, due probably to denaturing conditions used during purification, that were necessary considering that both the full length and the short sequence of Hst3p were complexed to the bacterial molecular chaperon GroEL. To improve protein folding in bacterial host and avoid denaturing conditions for purification, I expressed and purified recombinant Hst3p from a bacterial system over-expressing some molecular chaperons. Once determined the enzymatic activity of recombinant protein, an enzymatic assay will be set up, useful to screen and select small molecules, potential inhibitor of the fungal sirtuin Hst3p, which could be used as antifungal compounds. [edited by Author]
XXXI ciclo
APA, Harvard, Vancouver, ISO, and other styles
3

Milstone, Zachary J. "Histone Deacetylase 1 and 2 are Essential for Early Cardiac Development." eScholarship@UMMS, 2019. https://escholarship.umassmed.edu/gsbs_diss/1014.

Full text
Abstract:
Congenital heart disease is the most common congenital anomaly, affecting approximately 1% of all live births each year. Although clinical interventions are improving, many affected infants do not survive to adulthood. Congenital cardiac defects originate from disturbances during development, making the study of mammalian cardiogenesis critical to improving outcomes for infants with congenital heart disease. Development of the mammalian heart involves epigenetically-driven specification and commitment of a diverse landscape of cardiac progenitors. Recent studies determined that chromatin modifying enzymes play a previously underappreciated role in the pathogenesis of congenital heart defects. This thesis investigates the functions of Hdac1 and Hdac2, highly homologous Class I histone deacetylases, during early murine cardiac development. We establish that Hdac1 and Hdac2 cooperatively regulate cardiogenesis in distinct cardiac progenitor populations during development. Together, our findings demonstrate that Hdac1 and Hdac2 are critical mediators of the earliest stages of mammalian cardiogenesis through a variety of spatiotemporally specific, redundant, and dose-sensitive roles and indicate they may play important roles in the pathogenesis of human congenital cardiac defects.
APA, Harvard, Vancouver, ISO, and other styles
4

PERI, CAROLINA. "STUDY OF THE ROLE OF CLASS I HISTONE DEACETYLASES IN DIFFERENTIATION, METABOLISM AND IMMUNOPHENOTYPE OF ADIPOSE TISSUE." Doctoral thesis, Università degli Studi di Milano, 2020. http://hdl.handle.net/2434/796664.

Full text
Abstract:
INTRODUCTION Epigenome modifications and metabolic dysregulation have been shown to be connected to disease states like obesity and to the associated comorbidities. Epigenome modifiers such as histone deacetylases are involved in the regulation of adipose tissue pathophysiology. However, their specific role in adipocyte differentiation is still a matter of research. Moreover, in obesity excessive accumulation of fat, especially in visceral depots, triggers a low-grade inflammation that is responsible of metabolic dysfunction. The action of immune cells within adipose tissue affects normal metabolic homeostasis. PREVIOUS RESULTS Previous in vitro results from our group showed that inhibition of class I HDACs with MS-275, during early stage of adipocyte differentiation, leads to reduction of lipid droplets size. This phenomenon was accompanied by increased expression of genes regarding adipocyte functionality, lipolysis and fatty acid β-oxidation. However, these events were not observed in terminally differentiated adipocytes. Moreover, in vivo studies showed that HDAC3, a member of class I HDACs, acts as a molecular brake of metabolic rewiring that supports browning in WAT. AIM of this thesis was to further elucidate how class I HDACs are involved in adipocyte differentiation and in determining the metabolic phenotype of pre-adipocytes. Moreover, we aimed to investigate the changes of immune cell populations at different time points of high fat feeding, to fully characterize the phenotypical consequences of Hdac3 ablation in mice. In parallel, we wanted to identify key pathways and early events evoked by Hdac3 gene inactivation through transcriptomic and epigenomic analysis. RESULTS In vitro experiments on adipocytes precursors treated with MS-275 at the beginning of differentiation showed increased expression of genes belonging to mitochondrial activity and browning, which was accompanied by increased H3K27 acetylation of Pparg and Ucp1 gene enhancers. In vivo studies in H3atKO mice, exposed to HFD for different periods (4, 9, 16 weeks, respectively), showed changes in immune cell populations. The number of total macrophages significantly increased in epiWAT of H3atKO mice compared to control floxed (FL) mice at all the three periods of treatment. Moreover, H3atKO mice were able to maintain higher ratio of M2 pro-resolving vs M1 pro-inflammatory macrophages from 4 through 16 weeks of HFD feeding. In H3atKO mice fed LFD for 4 weeks we found upregulation of pathways regarding the futile cycle of simultaneous fatty acid synthesis and β-oxidation. Moreover, KO_LFD vs FL_LFD mice shown upregulation of pathways such as ferroptosis, amino acid biosynthesis and valine, leucine and isoleucine degradation pathways, while focal adhesion and extracellular receptor interaction were downregulated. One of the top downregulated gene was neuronatin (Nnat); we found a hypoacetylated region upstream the Nnat TSS. CONCLUSIONS In vitro results provided evidences regarding the role of class I HDACs in adipocyte differentiation. Their inhibition at the beginning of differentiation promotes an epigenetic imprinting towards oxidative and brown-like phenotype. In vivo experiments revealed that mice lacking Hdac3 were able to maintain a higher ratio of M2 vs M1 macrophages during an inflammatory stimulus such as HFD feeding. Such feature could support a pro-resolving inflammatory process. Omic analysis confirmed the futile cycle of fatty acid metabolism previously observed in our H3atKO model and highlighted interesting new pathways that better characterize H3atKO mice.
APA, Harvard, Vancouver, ISO, and other styles
5

Amaya, Maria. "The Role of the Nucleosome Remodeling and Histone Deacetylase (NuRD) Complex in Fetal γ-Globin Expression." VCU Scholars Compass, 2013. http://scholarscompass.vcu.edu/etd/521.

Full text
Abstract:
An understanding of the human fetal to adult hemoglobin switch offers the potential to ameliorate β-type globin gene disorders such as sickle cell anemia and β-thalassemia through activation of the fetal γ-globin gene. Chromatin modifying complexes, including MBD2-NuRD and GATA-1/FOG-1/NuRD play a role in γ-globin gene silencing, and Mi2β (CHD4) is a critical component of NuRD complexes. In the studies presented in Chapter 2, we observed that the absence of MBD2 in a sickle cell mouse model leads to a decrease in the number of sickled cells observed in the peripheral blood, and significantly increases survival in these mice. Although further studies will be necessary to fully understand the effect of MBD2 knockout in sickle cell disease mice, absence of MBD2 appears to partially ameliorate the sickle cell anemia phenotype in vivo. In the studies presented in Chapter 3, we observed that knockdown of Mi2β relieves γ-globin gene silencing in β-YAC transgenic murine CID hematopoietic cells and in CD34+ progenitor derived human primary adult erythroid cells. We show that independent of MBD2-NuRD and GATA-1/FOG-1/NuRD, Mi2β binds directly to and positively regulates both the KLF1 and BCL11A genes, which encode transcription factors critical for γ-globin gene silencing during β-type globin gene switching. Remarkably, less than 50% knockdown of Mi2β is sufficient to significantly induce γ-globin gene expression without disrupting erythroid differentiation of primary human CD34+ progenitors. These results indicate that Mi2β is a potential target for therapeutic induction of fetal hemoglobin.
APA, Harvard, Vancouver, ISO, and other styles
6

Robinson, Autumn Rose. "Investigating the Regulation and Roles of Histone Acetylase and Deacetylase Enzymes for Cellular Proliferation and the Adenovirus Life Cycle." Miami University / OhioLINK, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=miami1595965181848835.

Full text
APA, Harvard, Vancouver, ISO, and other styles
7

Lewandowski, Sara L. "Histone Deacetylase 3 Coordinates Heart Development Through Stage-Specific Roles in Cardiac Progenitor Cells." eScholarship@UMMS, 2012. http://escholarship.umassmed.edu/gsbs_diss/883.

Full text
Abstract:
Disruptions in cardiac development cause congenital heart disease, the most prevalent and deadly congenital malformation. Genetic and environmental factors are thought to contribute to these defects, however molecular mechanisms remain largely undefined. Recent work highlighted potential roles of chromatin- modifying enzymes in congenital heart disease pathogenesis. Histone deacetylases, a class of chromatin-modifying enzymes, have developmental importance and recognized roles in the mature heart. This thesis aimed to characterize functions of Hdac3 in cardiac development. We found loss of Hdac3 in the primary heart field causes precocious progenitor cell differentiation, resulting in hypoplastic ventricular walls, ventricular septal defect, and mid- gestational lethality. In primary heart field progenitors, Hdac3 interacts with, deacetylates, and functionally suppresses transcription factor Tbx5. Furthermore, a disease-associated Tbx5 mutation disrupts this interaction, rendering Tbx5 hyperacetylated and hyperactive. By contrast, deletion of Hdac3 in second heart field progenitors bypasses these defects, instead causing malformations in the outflow tract and semilunar valves, with lethality prior to birth. Affected semilunar valves and outflow tract vessels exhibit extracellular matrix and EndMT defects and activation of the Tgfβ1 signaling pathway. In normal second heart field development, Hdac3 represses Tgfβ1 transcription, independent of its deacetylase activity, by recruiting the PRC2 methyltransferase complex to methylate the Tgfβ1 promoter. Importantly, knockouts of Hdac3 in differentiated cardiac cells do not fully recapitulate the progenitor-specific knockout phenotypes. These results illustrate spatiotemporal roles of Hdac3, both deacetylase-dependent and deacetylase-independent, in cardiac development, suggesting that dysregulation of Hdac3 in cardiac progenitor cells could be a contributing factor in congenital heart disease pathogenesis.
APA, Harvard, Vancouver, ISO, and other styles
8

Lewandowski, Sara L. "Histone Deacetylase 3 Coordinates Heart Development Through Stage-Specific Roles in Cardiac Progenitor Cells." eScholarship@UMMS, 2016. https://escholarship.umassmed.edu/gsbs_diss/883.

Full text
Abstract:
Disruptions in cardiac development cause congenital heart disease, the most prevalent and deadly congenital malformation. Genetic and environmental factors are thought to contribute to these defects, however molecular mechanisms remain largely undefined. Recent work highlighted potential roles of chromatin- modifying enzymes in congenital heart disease pathogenesis. Histone deacetylases, a class of chromatin-modifying enzymes, have developmental importance and recognized roles in the mature heart. This thesis aimed to characterize functions of Hdac3 in cardiac development. We found loss of Hdac3 in the primary heart field causes precocious progenitor cell differentiation, resulting in hypoplastic ventricular walls, ventricular septal defect, and mid- gestational lethality. In primary heart field progenitors, Hdac3 interacts with, deacetylates, and functionally suppresses transcription factor Tbx5. Furthermore, a disease-associated Tbx5 mutation disrupts this interaction, rendering Tbx5 hyperacetylated and hyperactive. By contrast, deletion of Hdac3 in second heart field progenitors bypasses these defects, instead causing malformations in the outflow tract and semilunar valves, with lethality prior to birth. Affected semilunar valves and outflow tract vessels exhibit extracellular matrix and EndMT defects and activation of the Tgfβ1 signaling pathway. In normal second heart field development, Hdac3 represses Tgfβ1 transcription, independent of its deacetylase activity, by recruiting the PRC2 methyltransferase complex to methylate the Tgfβ1 promoter. Importantly, knockouts of Hdac3 in differentiated cardiac cells do not fully recapitulate the progenitor-specific knockout phenotypes. These results illustrate spatiotemporal roles of Hdac3, both deacetylase-dependent and deacetylase-independent, in cardiac development, suggesting that dysregulation of Hdac3 in cardiac progenitor cells could be a contributing factor in congenital heart disease pathogenesis.
APA, Harvard, Vancouver, ISO, and other styles
9

Arndt, David L. "Role of HDAC inhibition and environmental condition in altering phases of amphetamine self-administration." Diss., Kansas State University, 2016. http://hdl.handle.net/2097/32694.

Full text
Abstract:
Doctor of Philosophy
Psychological Sciences
Mary E. Cain
Gene-environment interactions play a significant role in drug abuse and addiction. Epigenetics (the study of how environmental stimuli alter gene expression) has gained attention in recent years as a significant contributor to many behavioral phenotypes of drug addiction. The current study sought to determine if differential rearing conditions can alter a specific epigenetic mechanism, histone deacetylase (HDAC), and how HDAC inhibition can affect drug-taking and drug-seeking behaviors differently among enriched, isolated, or standard-housed rats. Ninety male Sprague-Dawley rats were reared for 30 days in enriched (EC), isolated (IC), or standard (SC) conditions prior to amphetamine (0.03, 0.05, 0.1 mg/kg/infusion, i.v.) self-administration, extinction, or reinstatement sessions. Trichostatin A (TsA; 0.3 mg/kg, i.v.), an HDAC inhibitor, was injected 30 min prior to drug-taking or drug-seeking sessions. Results indicated that EC rats self-administered less amphetamine (0.03 mg/kg/infusion) than IC rats. No significant effects of TsA administration were found on general self-administration for any of the three amphetamine doses. While enrichment facilitated the extinction of active lever pressing, there was also a mild facilitation of extinction in IC-TsA rats compared to IC-vehicle counterparts. Lastly, TsA administration decreased cue-, but not drug-induced reinstatement, with IC-TsA rats exhibiting significantly attenuated cue-induced reinstatement compared to IC-vehicle rats. These findings suggest that differential rearing can alter HDAC mechanisms that can change drug-seeking behaviors, particularly in rats reared in isolated conditions. While TsA-induced HDAC inhibition may be less protective against general amphetamine self-administration, it may decrease drug-seeking tendencies during relapse that are induced by the reintroduction of contextual environmental cues heavily associated with drug reward.
APA, Harvard, Vancouver, ISO, and other styles
10

Saha, Bratati. "Identification and Validation of Small Molecules Inhibiting Human Adenovirus Replication." Thesis, Université d'Ottawa / University of Ottawa, 2019. http://hdl.handle.net/10393/39677.

Full text
Abstract:
Human adenovirus (HAdV) mainly causes minor illnesses, but can lead to severe disease and death in both immunocompromised and immunocompetent patients. In such cases, the current standards of treatment often do not improve disease outcome and no approved antiviral therapy against HAdV exists. Since HAdV relies on cellular machinery to assist in the progression of the virus lifecycle, we hypothesized that small molecules targeting certain cellular proteins/pathways, without severely affecting cell health, may serve as effective anti-HAdV compounds. Thus, we aimed to identify novel inhibitors of HAdV, and investigate the molecular mechanism to determine new therapeutic targets for intervention in HAdV infection. We first examined the antiviral properties of pan-histone deacetylase (HDAC) inhibitor SAHA and found that the drug affects multiple stages of the HAdV lifecycle, resulting in significant reductions in virus yield. SAHA was effective in decreasing gene expression from clinically relevant HAdV serotypes. Subsequent investigations on the role of HDACs in HAdV infection led us to determine that class I HDAC activity, mainly HDAC2, is necessary for optimal viral gene expression. Using a wildtype-like HAdV reporter construct that allows us to monitor virus replication by fluorescence microscopy, we then designed an efficient system for screening small molecules to identify novel HAdV inhibitors. We screened over 1300 small molecules, and the screen was sensitive enough to detect compounds with both robust and modest antiviral activity. Several positive hits were validated to reduce HAdV gene expression and yield from infected cells. Further investigation on the efficacy of these compounds and the mechanism behind their inhibition of HAdV can lead to the discovery of new pharmacological targets and the development of more effective antivirals.
APA, Harvard, Vancouver, ISO, and other styles
More sources

Books on the topic "Epigenetics: histone deacetylase"

1

Soares, Christiane Pienna, Jean Leandro Dos Santos, and Ângela Sousa, eds. Epigenetic Therapy with Histone Deacetylase Inhibitors: Implications for Cancer Treatment. Frontiers Media SA, 2021. http://dx.doi.org/10.3389/978-2-88966-835-9.

Full text
APA, Harvard, Vancouver, ISO, and other styles

Book chapters on the topic "Epigenetics: histone deacetylase"

1

Wong, Vincent Wai-Sun, Myth Tsz-Shun Mok, and Alfred Sze-Lok Cheng. "Histone Deacetylase HDAC8 and Insulin Resistance." In Handbook of Nutrition, Diet, and Epigenetics, 405–21. Cham: Springer International Publishing, 2019. http://dx.doi.org/10.1007/978-3-319-55530-0_23.

Full text
APA, Harvard, Vancouver, ISO, and other styles
2

Wong, Vincent Wai-Sun, Myth Tsz-Shun Mok, and Alfred Sze-Lok Cheng. "Histone Deacetylase HDAC8 and Insulin Resistance." In Handbook of Nutrition, Diet, and Epigenetics, 1–16. Cham: Springer International Publishing, 2017. http://dx.doi.org/10.1007/978-3-319-31143-2_23-1.

Full text
APA, Harvard, Vancouver, ISO, and other styles
3

Ganai, Shabir Ahmad. "Epigenetics and its Implications in Neurological Disorders." In Histone Deacetylase Inhibitors — Epidrugs for Neurological Disorders, 1–10. Singapore: Springer Singapore, 2019. http://dx.doi.org/10.1007/978-981-13-8019-8_1.

Full text
APA, Harvard, Vancouver, ISO, and other styles
4

Labrie, Viviane. "Histone Deacetylase Inhibitors: A Novel Therapeutic Approach for Cognitive Disorders." In Brain, Behavior and Epigenetics, 245–66. Berlin, Heidelberg: Springer Berlin Heidelberg, 2011. http://dx.doi.org/10.1007/978-3-642-17426-1_12.

Full text
APA, Harvard, Vancouver, ISO, and other styles
5

Heidor, Renato, Ernesto Vargas-Mendez, and Fernando Salvador Moreno. "Histone Deacetylase Inhibitor Tributyrin and Vitamin A in Cancer." In Handbook of Nutrition, Diet, and Epigenetics, 1615–36. Cham: Springer International Publishing, 2019. http://dx.doi.org/10.1007/978-3-319-55530-0_72.

Full text
APA, Harvard, Vancouver, ISO, and other styles
6

Heidor, Renato, Ernesto Vargas-Mendez, and Fernando Salvador Moreno. "Histone Deacetylase Inhibitor Tributyrin and Vitamin A in Cancer." In Handbook of Nutrition, Diet, and Epigenetics, 1–23. Cham: Springer International Publishing, 2017. http://dx.doi.org/10.1007/978-3-319-31143-2_72-1.

Full text
APA, Harvard, Vancouver, ISO, and other styles
7

Gray, Steven G. "Histone Deacetylase Inhibitors as a Therapeutic Modality in Multiple Sclerosis." In The Epigenetics of Autoimmune Diseases, 403–32. Chichester, UK: John Wiley & Sons, Ltd, 2009. http://dx.doi.org/10.1002/9780470743553.ch23.

Full text
APA, Harvard, Vancouver, ISO, and other styles
8

Treszl, András, Gergó Mészáros, Gergely Toldi, and Barna Vásárhelyi. "Histone Deacetylases and Autoimmunity." In The Epigenetics of Autoimmune Diseases, 385–402. Chichester, UK: John Wiley & Sons, Ltd, 2009. http://dx.doi.org/10.1002/9780470743553.ch22.

Full text
APA, Harvard, Vancouver, ISO, and other styles
9

Ahmad Ganai, Shabir. "Abridgement of Classical Histone Deacetylases, Their Inhibitors and Jeopardy of Synthetic Histone Deacetylase Inhibitors." In Natural HDAC Inhibitors for Epigenetic Combating of Cancer Progression, 1–8. New York: CRC Press, 2022. http://dx.doi.org/10.1201/9781003294863-1.

Full text
APA, Harvard, Vancouver, ISO, and other styles
10

Ganai, Shabir Ahmad. "Overview of Epigenetic Signatures and Their Regulation by Epigenetic Modification Enzymes." In Histone Deacetylase Inhibitors in Combinatorial Anticancer Therapy, 1–33. Singapore: Springer Singapore, 2020. http://dx.doi.org/10.1007/978-981-15-8179-3_1.

Full text
APA, Harvard, Vancouver, ISO, and other styles

Conference papers on the topic "Epigenetics: histone deacetylase"

1

Ismail, Houssam, Martine Bail, David Laperrière, Khalid Hilmi, and Sylvie Mader. "Abstract A55: Histone deacetylase inhibitors as differentiation agents in breast cancer cells." In Abstracts: AACR Special Conference on Chromatin and Epigenetics in Cancer - June 19-22, 2013; Atlanta, GA. American Association for Cancer Research, 2013. http://dx.doi.org/10.1158/1538-7445.cec13-a55.

Full text
APA, Harvard, Vancouver, ISO, and other styles
2

Gryder, Berkley E., Michelle J. Akbashev, Michael K. Rood, Paulette Dillard, Shafiq Khan, and Adegboyega K. Oyelere. "Abstract B50: Selectively targeting prostate cancer with antiandrogen-equipped histone deacetylase inhibitors." In Abstracts: AACR Special Conference on Chromatin and Epigenetics in Cancer - June 19-22, 2013; Atlanta, GA. American Association for Cancer Research, 2013. http://dx.doi.org/10.1158/1538-7445.cec13-b50.

Full text
APA, Harvard, Vancouver, ISO, and other styles
3

Tapadar, Subhasish, Idris Raji, Shaghayegh Fathi, Celinah Mwakwari, Eric Raftery, and Adegboyega K. Oyelere. "Abstract B57: Non-peptide macrocyclic histone deacetylase inhibitors: A structure activity relationship study." In Abstracts: AACR Special Conference on Chromatin and Epigenetics in Cancer - June 19-22, 2013; Atlanta, GA. American Association for Cancer Research, 2013. http://dx.doi.org/10.1158/1538-7445.cec13-b57.

Full text
APA, Harvard, Vancouver, ISO, and other styles
4

Cody, James J., James M. Markert, and Douglas R. Hurst. "Abstract B54: Treatment of breast cancer cells with histone deacetylase inhibitors increases the replication of an oncolytic herpes simplex virus." In Abstracts: AACR Special Conference on Chromatin and Epigenetics in Cancer - June 19-22, 2013; Atlanta, GA. American Association for Cancer Research, 2013. http://dx.doi.org/10.1158/1538-7445.cec13-b54.

Full text
APA, Harvard, Vancouver, ISO, and other styles
5

Wilson, Andrew J., Jeanette Saskowski, and Dineo Khabele. "Abstract B37: The histone deacetylase inhibitor panobinostat sensitizes cyclin E-amplified ovarian cancer cells to poly ADP ribose polymerase inhibitors via E2F1 downregulation." In Abstracts: AACR Special Conference: Chromatin and Epigenetics in Cancer; September 24-27, 2015; Atlanta, GA. American Association for Cancer Research, 2016. http://dx.doi.org/10.1158/1538-7445.chromepi15-b37.

Full text
APA, Harvard, Vancouver, ISO, and other styles
6

Limpaiboon, Temduang, and Ruethairat Sriraksa. "Abstract 1004: Histone deacetylase inhibitors: Potential epigenetic therapeutic drugs for cholangiocarcinoma." In Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC. American Association for Cancer Research, 2013. http://dx.doi.org/10.1158/1538-7445.am2013-1004.

Full text
APA, Harvard, Vancouver, ISO, and other styles
7

Weiss, Kurt R., Xiaodong Mu, and Daniel Brynien. "Abstract 5378: Epigenetic regugulation of osteosarcoma metastatic phenotype via histone deacetylace inhibition." In Proceedings: AACR 106th Annual Meeting 2015; April 18-22, 2015; Philadelphia, PA. American Association for Cancer Research, 2015. http://dx.doi.org/10.1158/1538-7445.am2015-5378.

Full text
APA, Harvard, Vancouver, ISO, and other styles
8

Liang, Gaoyang, Ruth Yu, Christopher Liddle, Morgan Truitt, Corina Antal, Annette Atkins, Ester Banayo, Michael Downes, and Ronald Evans. "Abstract 5065: Harnessing epigenetic reprogramming by histone deacetylase inhibitor MS275 for pancreatic cancer therapy." In Proceedings: AACR Annual Meeting 2017; April 1-5, 2017; Washington, DC. American Association for Cancer Research, 2017. http://dx.doi.org/10.1158/1538-7445.am2017-5065.

Full text
APA, Harvard, Vancouver, ISO, and other styles
9

Lopez, Gonzalo, Yechun Song, Dennis Ruder, Chad Creighton Creighton, Svetlana Bolshakov, Xiaoli Zhang, Dina Lev, and Raphael Pollock. "Abstract LB-251: Histone deacetylase inhibition for the treatment of epithelioid sarcoma; novel cross talk between epigenetic components." In Proceedings: AACR 106th Annual Meeting 2015; April 18-22, 2015; Philadelphia, PA. American Association for Cancer Research, 2015. http://dx.doi.org/10.1158/1538-7445.am2015-lb-251.

Full text
APA, Harvard, Vancouver, ISO, and other styles
10

Bhinder, Arvinder, Vivek Varma, Besma Abbaoui, Steven K. Clinton, and Amir Mortazavi. "Abstract 5430: Epigenetic targeting by histone deacetylase inhibitors reduces viability and induces apoptosis in human embryonal carcinoma cells." In Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DC. American Association for Cancer Research, 2010. http://dx.doi.org/10.1158/1538-7445.am10-5430.

Full text
APA, Harvard, Vancouver, ISO, and other styles
You might also be interested in the extended bibliographies on the topic 'Epigenetics: histone deacetylase' for particular source types:
Journal articles Dissertations / Theses
We offer discounts on all premium plans for authors whose works are included in thematic literature selections. Contact us to get a unique promo code!

To the bibliography