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Open AccessJournal ArticleDOI

Class IIa HDACs - new insights into their functions in physiology and pathology.

Maribel Parra
- 01 May 2015 - 
- Vol. 282, Iss: 9, pp 1736-1744
TLDR
This review brings up to date the knowledge of the physiological and pathological functions of class IIa HDACs, focusing in particular on the most recent discoveries from in vivo studies of mouse model systems.
Abstract
HDAC4, 5, 7 and 9 constitute the class IIa histone deacetylases (HDACs) within the large family of protein deacetylases. Class IIa HDACs have unique features that distinguish them from other HDACs. They contain an N-terminal domain that is required for their interaction with tissue-specific transcription factors and recruitment to their target genes. The N-terminal domain on class IIa HDACs also bears conserved serine residues that undergo signal-dependent phosphorylation, which brings about nuclear export of the enzymes and de-repression of their targets. One of the most important aspects of class IIa HDACs is their expression in specific tissues and organs within the organism, where they have crucial roles in development and differentiation processes. This review brings up to date our knowledge of the physiological and pathological functions of class IIa HDACs, focusing in particular on the most recent discoveries from in vivo studies of mouse model systems.

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Citations
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Metabolic regulation of histone post-translational modifications

TL;DR: Recent studies of the molecular mechanisms involved in metabolic regulation of histone modifications are summarized and discussed and their biological significance are discussed.
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A short guide to histone deacetylases including recent progress on class II enzymes.

TL;DR: It is suggested that their unique structural features and low enzymatic activity are important features to consider when designing new, more selective HDAC inhibitors.
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Histone deacetylases (HDACs): Evolution, specificity, role in transcriptional complexes, and pharmacological actionability

TL;DR: A review on the recent knowledge accrued on the zinc-dependent HDAC protein family across different species, tissues, and human pathologies, specifically focusing on the role of HDAC inhibitors as anti-cancer agents.
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Regulation of class IIa HDAC activities: it is not only matter of subcellular localization

TL;DR: The key mechanisms that fine tune class IIa HDACs activities are discussed, which reflect the wide range of biological responses under the scrutiny of this gene family.
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Therapeutic targeting of miR-29b/HDAC4 epigenetic loop in multiple myeloma

TL;DR: It is demonstrated here that miR-29b specifically targets HDAC4 and highlighted that both molecules are involved in a functional loop, shedding light on a novel epigenetic circuitry regulating multiple myeloma cell growth and survival and open new avenues for miR -29b–based epi-therapeutic approaches in the treatment of this malignancy.
References
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Journal ArticleDOI

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Journal ArticleDOI

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The many roles of histone deacetylases in development and physiology: Implications for disease and therapy

TL;DR: In this article, the expression of many HDAC isoforms in eukaryotic cells raises questions about their possible specificity or redundancy, and whether they control global or specific programs of gene expression.
Journal ArticleDOI

Signal-dependent nuclear export of a histone deacetylase regulates muscle differentiation

TL;DR: It is suggested that nucleo-cytoplasmic trafficking of HDACs is involved in the control of cellular differentiation, and a mechanism for transcriptional regulation through signal- and differentiation-dependent nuclear export of a chromatin-remodelling enzyme is highlighted.
Journal ArticleDOI

Class II Histone Deacetylases Act as Signal-Responsive Repressors of Cardiac Hypertrophy

TL;DR: It is shown that class II HDACs are substrates for a stress-responsive kinase specific for conserved serines that regulate MEF2-HDAC interactions, and act as signal-responsive suppressors of the transcriptional program governing cardiac hypertrophy and heart failure.
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