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Histone deacetylases (HDACs): characterization of the classical HDAC family

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TLDR
In this paper, a comprehensive overview of the structure, function and tissue distribution of members of the classical histone deacetylase (HDAC) family, in order to gain insight into the regulation of gene expression through HDAC activity is presented.
Abstract
Transcriptional regulation in eukaryotes occurs within a chromatin setting, and is strongly influenced by the post-translational modification of histones, the building blocks of chromatin, such as methylation, phosphorylation and acetylation. Acetylation is probably the best understood of these modifications: hyperacetylation leads to an increase in the expression of particular genes, and hypoacetylation has the opposite effect. Many studies have identified several large, multisubunit enzyme complexes that are responsible for the targeted deacetylation of histones. The aim of this review is to give a comprehensive overview of the structure, function and tissue distribution of members of the classical histone deacetylase (HDAC) family, in order to gain insight into the regulation of gene expression through HDAC activity. SAGE (serial analysis of gene expression) data show that HDACs are generally expressed in almost all tissues investigated. Surprisingly, no major differences were observed between the expression pattern in normal and malignant tissues. However, significant variation in HDAC expression was observed within tissue types. HDAC inhibitors have been shown to induce specific changes in gene expression and to influence a variety of other processes, including growth arrest, differentiation, cytotoxicity and induction of apoptosis. This challenging field has generated many fascinating results which will ultimately lead to a better understanding of the mechanism of gene transcription as a whole.

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Epigenetic regulation of endothelial-cell-mediated vascular repair

TL;DR: The potential of using small molecules that modulate the activities of epigenetic enzymes to enhance the vascular repair function of endothelial cells and offer insight on potential strategies that may accelerate clinical applications are discussed.
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Sirtuins (histone deacetylases III) in the cellular response to DNA damage--facts and hypotheses.

Marcin Kruszewski, +1 more
- 21 Nov 2005 - 
TL;DR: A hypothetical mechanism of sirtuin participation in DSB repair is proposed, based on the assumption that activation of PARP at the sites of DNA strand breaks leads to a local increase in nicotinamide concentration, which inhibits sirtuins exactly at the site ofDNA strand break.
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Aminothiazoles as Potent and Selective Sirt2 Inhibitors: A Structure–Activity Relationship Study

TL;DR: This work rationalizes the unique features of the SirReals and probes the limits of modifications on this scaffold regarding inhibitor potency and presents a crystal structure of hSirt2 in complex with an optimized SirReal derivative that exhibits an improved in vitro activity.
Journal ArticleDOI

The capability of reprogramming the male chromatin after fertilization is dependent on the quality of oocyte maturation

TL;DR: Some pig IVM oocytes fail to acquire full remodelling competence which is independent from their ooplasmic ability to morphologically reorganize the sperm nucleus into PN, as demonstrated by the use of HDAC inhibitors and the abnormal distribution of the enzyme between the two PN in IVM zygotes.
Journal ArticleDOI

A series of novel, potent, and selective histone deacetylase inhibitors.

TL;DR: A structurally novel series of HDAC inhibitors based on the natural cyclic tetrapeptide Apicidin is described, equipotent to current clinical candidates.
References
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Journal ArticleDOI

The language of covalent histone modifications.

TL;DR: It is proposed that distinct histone modifications, on one or more tails, act sequentially or in combination to form a ‘histone code’ that is, read by other proteins to bring about distinct downstream events.
Journal ArticleDOI

The fundamental role of epigenetic events in cancer

TL;DR: This review discusses patterns of DNA methylation and chromatin structure in neoplasia and the molecular alterations that might cause them and/or underlie altered gene expression in cancer.
Journal ArticleDOI

HDAC6 is a microtubule-associated deacetylase

TL;DR: The results show that HDAC6 is the tubulin deacetylase, and provide evidence that reversible acetylation regulates important biological processes beyond histone metabolism and gene transcription, including microtubule-dependent cell motility.
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Histone deacetylases and cancer: causes and therapies.

TL;DR: Together, histone acetyltransferases and histone deacetylases determine the acetylation status of histones, and inhibitors of HDACs have been found to cause growth arrest, differentiation and/or apoptosis of many tumours cells by altering the transcription of a small number of genes.
Journal ArticleDOI

Potent and specific inhibition of mammalian histone deacetylase both in vivo and in vitro by trichostatin A.

TL;DR: Results clearly indicate that TSA is a potent and specific inhibitor of the histone deacetylase and that the in vivo effect of TSA on cell proliferation and differentiation can be attributed to the inhibition of the enzyme.
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