Histone deacetylases (HDACs): characterization of the classical HDAC family
Annemieke J.M. de Ruijter,Albert H. van Gennip,Huib N. Caron,Stephan Kemp,André B.P. van Kuilenburg +4 more
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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.read more
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Epigenetic regulation of endothelial-cell-mediated vascular repair
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Sirtuins (histone deacetylases III) in the cellular response to DNA damage--facts and hypotheses.
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Aminothiazoles as Potent and Selective Sirt2 Inhibitors: A Structure–Activity Relationship Study
Matthias Schiedel,Tobias Rumpf,Berin Karaman,Attila Lehotzky,Judit Oláh,Stefan Gerhardt,Judit Ovádi,Wolfgang Sippl,Oliver Einsle,Manfred Jung +9 more
TL;DR: This work rationalizes the unique features of the SirReals and probes the limits of modifications on this scaffold regarding inhibitor potency and presents a crystal structure of hSirt2 in complex with an optimized SirReal derivative that exhibits an improved in vitro activity.
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The capability of reprogramming the male chromatin after fertilization is dependent on the quality of oocyte maturation
Luisa Gioia,Barbara Barboni,M. Turriani,Giulia Capacchietti,M. G. Pistilli,Paolo Berardinelli,Mauro Mattioli +6 more
TL;DR: Some pig IVM oocytes fail to acquire full remodelling competence which is independent from their ooplasmic ability to morphologically reorganize the sperm nucleus into PN, as demonstrated by the use of HDAC inhibitors and the abnormal distribution of the enzyme between the two PN in IVM zygotes.
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A series of novel, potent, and selective histone deacetylase inhibitors.
Philip Jones,Sergio Altamura,Prasun K. Chakravarty,Ottavia Cecchetti,Raffaele De Francesco,Paola Gallinari,Raffaele Ingenito,Peter T. Meinke,Alessia Petrocchi,Michael Rowley,Rita Scarpelli,Sergio Serafini,Christian Steinkühler +12 more
TL;DR: A structurally novel series of HDAC inhibitors based on the natural cyclic tetrapeptide Apicidin is described, equipotent to current clinical candidates.
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