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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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X-linked adrenoleukodystrophy: very long-chain fatty acid metabolism, ABC half-transporters and the complicated route to treatment.

TL;DR: Over-expression of ALDRP can correct the biochemical defect both in X-ald patients cells and the Abcd1 knockout mouse, providing an exciting new possibility for treatment of X-ALD patients.
Journal ArticleDOI

Organ-specific requirements for Hdac1 in liver and pancreas formation

TL;DR: The genetic studies demonstrate that Hdac1 is crucial for regulating distinct steps in endodermal organogenesis and establish zebrafish as a tractable system to investigate chromatin remodelling factor functions in controlling gene expression programmes in vertebrate endoder mal organogenesis.
Journal ArticleDOI

Selective histone deacetylase small molecule inhibitors: recent progress and perspectives.

TL;DR: A considerable achievement of development of isoform- or class-selective HDAC inhibitors has been made, yielding many drug candidates for further clinical studies, which represents a state-of-the-art technology in the drug discovery arena.
Journal ArticleDOI

Redox Regulation of Histone Deacetylases and Glucocorticoid-Mediated Inhibition of the Inflammatory Response

TL;DR: Oxidative stress can enhance inflammatory gene expression by further stimulating AP-1- and NF-kappaB-mediated gene expression and elevating histone acetylation, and oxidant stress, acting through changes in chromatin structure, can enhance inflammation and induce a state of relative glucocorticoid insensitivity.
Journal ArticleDOI

Acetylation of insulin receptor substrate-1 is permissive for tyrosine phosphorylation

Christina Kaiser, +1 more
- 02 Nov 2004 - 
TL;DR: The results show that IRS-1 is an acetylated protein, a post-translational modification that has not been previously described, of which the acetylation is increased by treatment of cells with Trichostatin A (TSA), an inhibitor of HDAC activity.
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.
Journal ArticleDOI

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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