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
Citations
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Drug Insight: histone deacetylase inhibitor-based therapies for cutaneous T-cell lymphomas.
Omar Khan,Nicholas B. La Thangue +1 more
TL;DR: Recent developments in the understanding of the molecular events that underlie the anticancer effects of HDAC inhibitors are discussed, and this information is related to the emerging clinical picture for the treatment of cutaneous T-cell lymphoma and related malignancies.
Journal ArticleDOI
Small Molecule Inhibitors of Zinc-dependent Histone Deacetylases
TL;DR: Continued development and characterization of highly optimized small molecule inhibitors of HDAC enzymes will help refine the understanding of their function and, optimistically, lead to novel therapeutic treatment alternatives for a host of neurological disorders.
Journal ArticleDOI
Correlation between MMP-13 and HDAC7 expression in human knee osteoarthritis
Reiji Higashiyama,Shigeru Miyaki,Satoshi Yamashita,Teruhito Yoshitaka,Görel Lindman,Yoshiaki Ito,Takahisa Sasho,Kazuhisa Takahashi,Martin Lotz,Hiroshi Asahara +9 more
TL;DR: Elevated HDAC7 expression in human OA may contribute to cartilage degradation via promoting MMP-13 gene expression, suggesting the critical role of M MP-13 in OA pathogenesis.
Journal ArticleDOI
Vascular histone deacetylation by pharmacological HDAC inhibition
Haloom Rafehi,Aneta Balcerczyk,Sebastian Lunke,Antony Kaspi,Mark Ziemann,Harikrishnan Kn,Jun Okabe,Ishant Khurana,Jenny Ying Ying Ooi,Abdul Waheed Khan,Xiao-Jun Du,Lisa Chang,Izhak Haviv,Samuel T. Keating,Tom C. Karagiannis,Assam El-Osta +15 more
TL;DR: This study provides an important framework for HDAC inhibitor function in vascular biology and a comprehensive description of genome-wide deacetylation by pharmacological HDAC inhibition.
Patent
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Stuart L. Schreiber,Scott M. Sternson,Jason C. Wong,Christina M. Grozinger,Stephen J. Haggarty,Kathryn M. Koeller +5 more
TL;DR: In this article, the authors present novel compounds of general formula (I): and pharmaceutically acceptable derivatives thereof, wherein R?1, R2, R3?, n, X and Y are as defined herein.
References
More filters
Journal ArticleDOI
The language of covalent histone modifications.
Brian D. Strahl,C D Allis +1 more
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
Peter A. Jones,Stephen B. Baylin +1 more
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
Charlotte Hubbert,Amaris Guardiola,Rong Shao,Yoshiharu Kawaguchi,Akihiro Ito,Andrew B. Nixon,Minoru Yoshida,Xiao-Fan Wang,Tso-Pang Yao +8 more
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.
Paul A. Marks,Richard A. Rifkind,Victoria M. Richon,Ronald Breslow,Thomas E. Miller,William Kevin Kelly +5 more
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.