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Molecules and Cells Oct 2020Histone acetylation and deacetylation play central roles in the regulation of chromatin structure and transcription by RNA polymerase II (RNA Pol II). Although Hda1... (Review)
Review
Histone acetylation and deacetylation play central roles in the regulation of chromatin structure and transcription by RNA polymerase II (RNA Pol II). Although Hda1 histone deacetylase complex (Hda1C) is known to selectively deacetylate histone H3 and H2B to repress transcription, previous studies have suggested its potential roles in histone H4 deacetylation. Recently, we have shown that Hda1C has two distinct functions in histone deacetylation and transcription. Histone H4-specific deacetylation at highly transcribed genes negatively regulates RNA Pol II elongation and H3 deacetylation at inactive genes fine-tunes the kinetics of gene induction upon environmental changes. Here, we review the recent understandings of transcriptional regulation via histone deacetylation by Hda1C. In addition, we discuss the potential mechanisms for histone substrate switching by Hda1C, depending on transcriptional frequency and activity.
Topics: Acetylation; Animals; Histone Deacetylase 1; Histones; Humans; Promoter Regions, Genetic; RNA Polymerase II; Transcription, Genetic; Yeasts
PubMed: 32913143
DOI: 10.14348/molcells.2020.0141 -
Journal of Experimental Botany Aug 2020As sessile organisms, plants face versatile environmental challenges and require proper responses at multiple levels for survival. Epigenetic modification of DNA and... (Review)
Review
As sessile organisms, plants face versatile environmental challenges and require proper responses at multiple levels for survival. Epigenetic modification of DNA and histones is a conserved gene-regulatory mechanism and plays critical roles in diverse aspects of biological processes, ranging from genome defense and imprinting to development and physiology. In recent years, emerging studies have revealed the interplay between signaling transduction pathways, epigenetic modifications, and chromatin cascades. Specifically, histone acetylation and deacetylation dictate plant responses to environmental cues by modulating chromatin dynamics to regulate downstream gene expression as signaling outputs. In this review, we summarize current understandings of the link between plant signaling pathways and epigenetic modifications with a focus on histone acetylation and deacetylation.
Topics: Acetylation; Epigenesis, Genetic; Histone Deacetylases; Histones; Plants
PubMed: 32333777
DOI: 10.1093/jxb/eraa202 -
International Journal of Molecular... Oct 2023Ovarian cancer is the most lethal gynecologic malignancy, and metastasis is the major cause of death in patients with ovarian cancer, which is regulated by the... (Review)
Review
Ovarian cancer is the most lethal gynecologic malignancy, and metastasis is the major cause of death in patients with ovarian cancer, which is regulated by the coordinated interplay of genetic and epigenetic mechanisms. Histone deacetylases (HDACs) are enzymes that can catalyze the deacetylation of histone and some non-histone proteins and that are involved in the regulation of a variety of biological processes via the regulation of gene transcription and the functions of non-histone proteins such as transcription factors and enzymes. Aberrant expressions of HDACs are common in ovarian cancer. Many studies have found that HDACs are involved in regulating a variety of events associated with ovarian cancer metastasis, including cell migration, invasion, and the epithelial-mesenchymal transformation. Herein, we provide a brief overview of ovarian cancer metastasis and the dysregulated expression of HDACs in ovarian cancer. In addition, we discuss the roles of HDACs in the regulation of ovarian cancer metastasis. Finally, we discuss the development of compounds that target HDACs and highlight their importance in the future of ovarian cancer therapy.
Topics: Humans; Female; Histone Deacetylases; Histone Deacetylase Inhibitors; Ovarian Neoplasms; Histones
PubMed: 37894746
DOI: 10.3390/ijms242015066 -
World Journal of Surgical Oncology Apr 2022This review systematically summarizes gene biology features and protein structure of nucleoplasmin2 (NPM2) and the relationship between NPM2 and malignant peritoneal... (Review)
Review
BACKGROUND
This review systematically summarizes gene biology features and protein structure of nucleoplasmin2 (NPM2) and the relationship between NPM2 and malignant peritoneal mesothelioma (MPM), in order to explore the molecular pathological mechanism of MPM and explore new therapeutic targets.
METHODS
NCBI PubMed database was used for the literature search. NCBI Gene and Protein databases, Ensembl Genome Browser, UniProt, and RCSB PDB database were used for gene and protein review. Three online tools (Consurf, DoGSiteScorer, and ZdockServer), the GEPIA database, and the Cancer Genome Atlas were used to analyze bioinformatics characteristics for NPM2 protein.
RESULTS
The main structural domains of NPM2 protein include the N-terminal core region, acidic region, and motif and disordered region. The N-terminal core region, involved in histone binding, is the most conserved domain in the nucleoplasmin (NPM) family. NPM2 with a large acidic tract in its C-terminal tail (NPM2-A2) is able to bind histones and form large complexes. Bioinformatics results indicated that NPM2 expression was correlated with the pathology of multiple tumors. Among mesothelioma patients, 5-year survival of patients with low-NPM2-expression was significantly higher than that of the high-NPM2-expression patients. NPM2 can facilitate the formation of histone deacetylation. NPM2 may promote histone deacetylation and inhibit the related-gene transcription, thus leading to abnormal proliferation, invasion, and metastasis of MPM.
CONCLUSION
NPM2 may play a key role in the development and progression of MPM.
Topics: Biology; Clinical Medicine; Histones; Humans; Mesothelioma; Nucleoplasmins
PubMed: 35490253
DOI: 10.1186/s12957-022-02604-3 -
EMBO Reports Jun 2022Primordial germ cells (PGCs) are the progenitor cells that give rise to sperm and eggs. Sinhcaf is a recently identified subunit of the Sin3 histone deacetylase complex...
Primordial germ cells (PGCs) are the progenitor cells that give rise to sperm and eggs. Sinhcaf is a recently identified subunit of the Sin3 histone deacetylase complex (SIN3A-HDAC). Here, we provide evidence that Sinhcaf-dependent histone deacetylation is essential for germ plasm aggregation and primordial germ cell specification. Specifically, maternal-zygotic sinhcaf zebrafish mutants exhibit germ plasm aggregation defects, decreased PGC abundance and male-biased sex ratio, which can be rescued by re-expressing sinhcaf. Overexpression of sinhcaf results in excess PGCs and a female-biased sex ratio. Sinhcaf binds to the promoter region of kif26ab. Loss of sinhcaf epigenetically switches off kif26ab expression by increasing histone 3 acetylation in the promoter region. Injection of kif26ab mRNA could partially rescue the germ plasm aggregation defects in sinhcaf mutant embryos. Taken together, we demonstrate a role of Sinhcaf in germ plasm aggregation and PGC specialization that is mediated by regulating the histone acetylation status of the kif26ab promoter to activate its transcription. Our findings provide novel insights into the function and regulatory mechanisms of Sinhcaf-mediated histone deacetylation in PGC specification.
Topics: Animals; Female; Germ Cells; Histones; Male; RNA, Messenger; Zebrafish; Zygote
PubMed: 35532311
DOI: 10.15252/embr.202154387 -
Cold Spring Harbor Perspectives in... Jul 2013Saccharomyces cerevisiae provides a well-studied model system for heritable silent chromatin, in which a nonhistone protein complex--the SIR complex--represses genes by... (Review)
Review
Saccharomyces cerevisiae provides a well-studied model system for heritable silent chromatin, in which a nonhistone protein complex--the SIR complex--represses genes by spreading in a sequence-independent manner, much like heterochromatin in higher eukaryotes. The ability to study mutations in histones and to screen genome-wide for mutations that impair silencing has yielded an unparalleled depth of detail about this system. Recent advances in the biochemistry and structural biology of the SIR-chromatin complex bring us much closer to a molecular understanding of how Sir3 selectively recognizes the deacetylated histone H4 tail and demethylated histone H3 core. The existence of appropriate mutants has also shown how components of the silencing machinery affect physiological processes beyond transcriptional repression.
Topics: Acetylation; DNA Replication; Evolution, Molecular; Gene Silencing; Heterochromatin; Histones; Models, Genetic; Saccharomyces cerevisiae; Silent Information Regulator Proteins, Saccharomyces cerevisiae
PubMed: 23818500
DOI: 10.1101/cshperspect.a017491 -
Journal of Thrombosis and Haemostasis :... Feb 2023Functioning as important hematologic cells for hemostasis, wound healing and immune defense platelets are produced before being released into the blood by cytoplasmic...
BACKGROUND
Functioning as important hematologic cells for hemostasis, wound healing and immune defense platelets are produced before being released into the blood by cytoplasmic fragmentation at the end of the megakaryocyte (MK) differentiation, during which the involvement of both apoptosis and autophagy has been reported. Inhibitory sialic acid-binding immunoglobulin-like lectin-7 gene (Siglec-7) can be expressed on platelets and induce apoptosis on activation for uncharacterized function.
OBJECTIVE
We aimed to investigate the regulatory mechanism for Siglec-7 activation along MK differentiation and its physiologic role during the MK maturation and platelet formation.
METHODS
By using 2 well-established MK differentiation models (HEL and K562) and human primary CD34 cell, we examined the upregulations of transcript and protein levels of Siglec-7 during MK differentiation, and the effect of Siglec-7 surface presence on MK differentiation and platelet-like particles (PLPs) release.
RESULTS
We show that both transcripts and surface Siglec-7 were elevated during MK differentiation, and the histone deacetylase 1 (HDAC1) acted as a negative regulator for Siglec-7 activation. By increasing Siglec-7 surface expression, we found that increased presence of Siglec-7 not only enhanced MK maturation but also the release of PLPs by activating caspase 3-dependent signaling, as evidenced in the observation of more CD41, polyploidy, and platelet factor 4 transcript formations.
CONCLUSION
In this study, we demonstrated that Siglec-7 activation was subjected to epigenetic regulation, and the resulting induced expression of surface Siglec-7 played an important regulatory role in promoting MK differentiation, maturation, and PLP formation.
Topics: Humans; Cell Differentiation; Epigenesis, Genetic; Histones; Megakaryocytes; Sialic Acid Binding Immunoglobulin-like Lectins
PubMed: 36700509
DOI: 10.1016/j.jtha.2022.11.007 -
Frontiers in Endocrinology 2020Over the past decade, the increasing prevalence of obesity and its associated metabolic disorders constitutes one of the most concerning healthcare issues for countries... (Review)
Review
Over the past decade, the increasing prevalence of obesity and its associated metabolic disorders constitutes one of the most concerning healthcare issues for countries worldwide. In an effort to curb the increased mortality and morbidity derived from the obesity epidemic, various therapeutic strategies have been developed by researchers. In the recent years, advances in the field of adipocyte biology have revealed that the thermogenic adipose tissue holds great potential in ameliorating metabolic disorders. Additionally, epigenetic research has shed light on the effects of histone acetylation on adipogenesis and thermogenesis, thereby establishing the essential roles which histone acetyltransferases (HATs) and histone deacetylases (HDACs) play in metabolism and systemic energy homeostasis. In regard to the therapeutic potential of thermogenic adipocytes for the treatment of metabolic diseases, herein, we describe the current state of knowledge of the regulation of thermogenic adipocyte differentiation and adaptive thermogenesis through histone acetylation. Furthermore, we highlight how different HATs and HDACs maintain the epigenetic transcriptional network to mediate the pathogenesis of various metabolic comorbidities. Finally, we provide insights into recent advances of the potential therapeutic applications and development of HAT and HDAC inhibitors to alleviate these pathological conditions.
Topics: Acetylation; Adaptation, Physiological; Adipocytes; Adipogenesis; Animals; Cell Differentiation; Histones; Humans; Thermogenesis
PubMed: 32174890
DOI: 10.3389/fendo.2020.00095 -
Epigenetic dysregulation in autophagy signaling as a driver of viral manifested oral carcinogenesis.Biochimica Et Biophysica Acta.... Nov 2022Concurrent viral infections insist on dysregulated epigenetics of tumor suppressor genes (TSGs), cell cycle regulators, apoptosis, and autophagy-associated genes to... (Review)
Review
BACKGROUND
Concurrent viral infections insist on dysregulated epigenetics of tumor suppressor genes (TSGs), cell cycle regulators, apoptosis, and autophagy-associated genes to manifest oral carcinogenesis. Autophagy has been projected as a strategic defense signaling cascade against viral entry and subsequent oral carcinogenesis. Compromised autophagy signaling during viral infection fuels oral cancer initiation and progression.
SCOPE OF REVIEW
The aberrant expression of autophagy genes and their encoded proteins is catalyzed by the dysregulated epigenome, legitimate epigenomic mutations, and post-transcriptional modifications such as hypermethylation, deacetylation of histone and non-histone targets, and hyperacetylation of histones that drive malignant transformation during oral carcinogenesis. Recent investigations have predicted epi-drugs (intriguingly methylation and deacetylation inhibitors and activators) as next-generation oral cancer therapeutic agents with a special notation for autophagy regulation.
MAJOR CONCLUSIONS
This review focuses on the epigenetic mediated post-transcriptional modulation of autophagy genes during viral manifested oral carcinogenesis with a distinctive perception of autophagy-modulating epi-drugs in oral cancer therapeutics.
Topics: Autophagy; Carcinogenesis; Epigenesis, Genetic; Epigenomics; Histones; Humans; Mouth Neoplasms
PubMed: 35940381
DOI: 10.1016/j.bbadis.2022.166517 -
Biochimica Et Biophysica Acta.... Oct 2020Acetylation belongs to a class of post-translational modification (PTM) processes that epigenetically regulate gene expression and gene transcriptional activity.... (Review)
Review
Acetylation belongs to a class of post-translational modification (PTM) processes that epigenetically regulate gene expression and gene transcriptional activity. Reversible histone acetylation on lysine residues governs the interactions between DNA and histones to mediate chromatin remodeling and gene transcription. Non-histone protein acetylation complicates cellular function whereas acetylation of key mitochondrial enzymes regulates bioenergetic metabolism. Acetylation and deacetylation of functional proteins are essential to the delicated homeostatic regulation of embryonic development, postnatal maturation, cardiomyocyte differentiation, cardiac remodeling and onset of various cardiovascular diseases including obesity, diabetes mellitus, cardiometabolic diseases, ischemia-reperfusion injury, cardiac remodeling, hypertension, and arrhythmias. Histone acetyltransferase (HATs) and histone deacetylases (HDACs) are essential enzymes mainly responsible for the regulation of lysine acetylation levels, thus providing possible drugable targets for therapeutic interventions in the management of cardiovascular diseases.
Topics: Acetylation; Animals; Cardiovascular Diseases; Cell Differentiation; Diabetes Mellitus; Energy Metabolism; Histone Acetyltransferases; Histone Deacetylases; Histones; Humans; Lysine; Obesity; Protein Processing, Post-Translational; Reperfusion Injury
PubMed: 32413386
DOI: 10.1016/j.bbadis.2020.165836