Histone deacetylases—an important class of cellular regulators with a variety of functions

Hildmann, Christian; Riester, Daniel; Schwienhorst, Andreas

doi:10.1007/s00253-007-0911-2

Cited by 166 publications

(132 citation statements)

References 143 publications

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“…Type A HATs are further divided into five classes based on the structural and functional differences (Grant and Berger, 1999). HDACs are mainly classified into four classes (Hildmann et al, 2007;Selvi and Kundu, 2009). Class I includes HDAC 1-3 and 8.…”

Section: Histone Acetylationmentioning

confidence: 99%

Epigenetics of the Depressed Brain: Role of Histone Acetylation and Methylation

Sun

Kennedy

Nestler

2012

Neuropsychopharmacol

341

233

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Major depressive disorder is a chronic, remitting syndrome involving widely distributed circuits in the brain. Stable alterations in gene expression that contribute to structural and functional changes in multiple brain regions are implicated in the heterogeneity and pathogenesis of the illness. Epigenetic events that alter chromatin structure to regulate programs of gene expression have been associated with depression-related behavior, antidepressant action, and resistance to depression or 'resilience' in animal models, with increasing evidence for similar mechanisms occurring in postmortem brains of depressed humans. In this review, we discuss recent advances in our understanding of epigenetic contributions to depression, in particular the role of histone acetylation and methylation, which are revealing novel mechanistic insight into the syndrome that may aid in the development of novel targets for depression treatment.

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Section: Histone Acetylationmentioning

confidence: 99%

Epigenetics of the Depressed Brain: Role of Histone Acetylation and Methylation

Sun

Kennedy

Nestler

2012

Neuropsychopharmacol

341

233

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“…Previous studies also suggest that transcriptional suppression of some genes may depend on DNA methylation or histone deacetylation of chromatin of their promoter regions (41)(42)(43). To explore whether TAZ-TEAD-induced ⌬Np63 transcriptional repression is due to chromosome methylation/ acetylation, we treated breast cancer cells with inhibitors of histone modification.…”

Section: Modulation Of Deacetylation Is Critical For Taz-tead-inducedmentioning

confidence: 99%

Hippo Component TAZ Functions as a Co-repressor and Negatively Regulates ΔNp63 Transcription through TEA Domain (TEAD) Transcription Factor

Valencia-Sama¹,

Zhao²,

Lai

et al. 2015

Journal of Biological Chemistry

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“…Deacetylation of histones alters the chromatin structure and represses transcription. Abnormal activity of these enzymes is implicated in several diseases, especially in cancer [20,23,31,98,107,136,159,[232][233][234][235][236][237][238].…”

Section: Class I Ii and Iv Deacetylasesmentioning

confidence: 99%

Modulation of Epigenetic Targets for Anticancer Therapy: Clinicopathological Relevance, Structural Data and Drug Discovery Perspectives

Andreoli¹,

Barbosa²,

Parenti³

et al. 2012

CPD

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Abstract:Research on cancer epigenetics has flourished in the last decade. Nevertheless growing evidence point on the importance to understand the mechanisms by which epigenetic changes regulate the genesis and progression of cancer growth. Several epigenetic targets have been discovered and are currently under validation for new anticancer therapies. Drug discovery approaches aiming to target these epigenetic enzymes with small-molecules inhibitors have produced the first pre-clinical and clinical outcomes and many other compounds are now entering the pipeline as new candidate epidrugs. The most studied targets can be ascribed to histone deacetylases and DNA methyltransferases, although several other classes of enzymes are able to operate post-translational modifications to histone tails are also likely to represent new frontiers for therapeutic interventions. By acknowledging that the field of cancer epigenetics is evolving with an impressive rate of new findings, with this review we aim to provide a current overview of pre-clinical applications of smallmolecules for cancer pathologies, combining them with the current knowledge of epigenetic targets in terms of available structural data and drug design perspectives.Keywords: Epigenetics, anticancer therapy, DNA methyltransferases, protein methyltransferases, demethylases, deacetylases, acetyltransferases, histone post-translational modifications, drug design, crystallography, small-molecule inhibitors. INTRODUCTIONThe term epigenetics currently refers to the mechanisms of temporal and spatial control of gene activity that do not depend on the DNA sequence, influencing the physiological and pathological development of an organism. The molecular mechanisms by which epigenetic changes occur are complex and cover a wide range of processes including paramutation, bookmarking, imprinting, gene silencing, carcinogenesis progression, and, most importantly, regulation of heterochromatin and histone modifications [1]. At a biochemical level, epigenetic alterations in chromatin involve methylation of DNA patterns, several forms of histone modifications and microRNA (miRNA) expression. All these processes modulate the structure of chromatin leading to the activation or silencing of gene expression [2][3][4][5][6]. More specifically, the chromatin remodeling is accomplished by two main mechanisms that concern the methylation of cytosine residues in DNA and a variety of post-translational modifications (PTMs) occurring at the N-terminal tails of histone proteins. These PTMs include acetylation, methylation, phosphorylation, ubiquitylation, sumoylation, glycosylation, ADPribosylation, carbonylation, citrullination and biotinylation [7,8]. Among all PTMs for example, histone tails can have its lysine residues acetylated, methylated or ubiquitilated; arginine can be methylated; serine and threonine residues can be phosphorylated [9][10][11][12][13][14][15][16][17]. These covalent modifications are able to cause other PTMs and the ensemble of this cross-talk is known as the his...

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Histone deacetylases—an important class of cellular regulators with a variety of functions

Cited by 166 publications

References 143 publications

Epigenetics of the Depressed Brain: Role of Histone Acetylation and Methylation

Epigenetics of the Depressed Brain: Role of Histone Acetylation and Methylation

Hippo Component TAZ Functions as a Co-repressor and Negatively Regulates ΔNp63 Transcription through TEA Domain (TEAD) Transcription Factor

Modulation of Epigenetic Targets for Anticancer Therapy: Clinicopathological Relevance, Structural Data and Drug Discovery Perspectives

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