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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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Regulation of cardiac hypertrophy by intracellular signalling pathways

TL;DR: Recent findings in genetically modified animal models implicate important intermediate signal-transduction pathways in the coordination of heart growth following physiological and pathological stimulation.
Journal ArticleDOI

Molecular evolution of the histone deacetylase family: functional implications of phylogenetic analysis.

TL;DR: Phylogenetic analysis of bacterial HDAC relatives suggests that all three HDAC classes precede the evolution of histone proteins and raises the possibility that the primary activity of some "histone deacetylase" enzymes is directed against non-histone substrates.
Journal ArticleDOI

Genome-wide Mapping of HATs and HDACs Reveals Distinct Functions in Active and Inactive Genes

TL;DR: In this paper, a genome-wide mapping of HATs and deacetylases binding on chromatin was performed and it was found that both are found at active genes with acetylated histones.
Journal ArticleDOI

Epigenetic protein families: a new frontier for drug discovery

TL;DR: The key protein families that mediate epigenetic signalling through the acetylation and methylation of histones are reviewed, including histone deacetylases, protein methyltransferases, lysine demethylases, bromodomain-containing proteins and proteins that bind to methylated histones.
Journal ArticleDOI

The Rpd3/Hda1 family of lysine deacetylases: from bacteria and yeast to mice and men.

TL;DR: In vertebrates, the Rpd3/Hda1 family contains 11 members, traditionally referred to as histone deacetylases (HDAC) 1–11, which are further grouped into classes I, II and IV.
References
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Journal ArticleDOI

The Histone Deacetylase Inhibitor Trichostatin A Derepresses the Telomerase Reverse Transcriptase (hTERT) Gene in Human Cells

TL;DR: In this paper, the authors demonstrate that the histone deacetylase (HDAC) inhibitor trichostatin A (TSA) induces hyperacetylation of histones at the telomerase reverse transcriptase (hTERT) proximal promoter.
Journal ArticleDOI

Inhibitors of human histone deacetylase: synthesis and enzyme and cellular activity of straight chain hydroxamates.

TL;DR: In this paper, analogues of suberoylanilide hydroxamic acid (SAHA) and trichostatin A have been used to induce terminal differentiation of human tumor cell lines and to have antitumor effects in vivo.
Journal Article

Combination of phenylbutyrate and 13-cis retinoic acid inhibits prostate tumor growth and angiogenesis

TL;DR: An additive inhibitory effect of combination of differentiation agents PB and CRA on prostate tumor growth through a direct effect on both tumor and endothelial cells is shown.
Journal Article

Carboxypeptidase A3 (CPA3): A Novel Gene Highly Induced by Histone Deacetylase Inhibitors during Differentiation of Prostate Epithelial Cancer Cells

TL;DR: It is found that the androgen-independent prostate cancer cell line PC-3 undergoes terminal differentiation and apoptosis after treatment with sodium butyrate (NaBu), and a novel cDNA designated carboxypeptidase A3 (CPA3), which was up-regulated in NaBu-treated PC- 3 cells, was identified and characterized.
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