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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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Blockade of histone deacetylase 6 protects against cisplatin-induced acute kidney injury.

TL;DR: Evidence is provided that HDAC6 inhibition is protective against cisplatin-induced acute kidney injury (AKI) and suggest thatHDAC6 may be a potential therapeutic target for AKI treatment.
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One-carbon metabolism and epigenetic regulation of embryo development

TL;DR: In this paper, the effects of 1C metabolism on epigenetic programming in mammalian gametes and the early embryo were investigated. But, the authors did not consider the effect of methyl donors (e.g., betaine) and 1C cofactors on the subsequent health and metabolism of offspring.
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Mitochondrial acetylation and diseases of aging.

TL;DR: The implications of mitochondrial acetylation for the aging process will be discussed, as well as its potential implications for the unique and localized metabolic states that occur during the aging-associated conditions of heart failure and cancer growth.
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Spiruchostatin A Inhibits Proliferation and Differentiation of Fibroblasts from Patients with Pulmonary Fibrosis

TL;DR: The concept that bicyclic tetrapeptide HDIs merit further investigation as potential treatments for IPF is supported, as Western blot analyses revealed that SpA caused a concentration-dependent increase in histone H3 acetylation, paralleling its antiproliferative effect.
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Comparison of trichostatin A and valproic acid treatment regimens in a mouse model of kidney fibrosis

TL;DR: Comparisons of the effect of two HDAC inhibitors, trichostatin A and valproic acid, in an experimental model of kidney fibrosis, confirm a role for HDACs in renal fibrogenesis and point towards a therapeutic potential forHDAC inhibitors.
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.
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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.
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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.
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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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