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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Microarray and comparative genomics-based identification of genes and gene regulatory regions of the mouse immune system
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Both HDAC5 and HDAC6 are required for the proliferation and metastasis of melanoma cells
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Identification of novel, selective, and stable inhibitors of class II histone deacetylases. Validation studies of the inhibition of the enzymatic activity of HDAC4 by small molecules as a novel approach for cancer therapy.
Jesus Maria Ontoria Ontoria,Sergio Altamura,Annalise Di Marco,Federica Ferrigno,Ralph Laufer,Ester Muraglia,Maria Cecilia Palumbi,Michael Rowley,Rita Scarpelli,Carsten Schultz-Fademrecht,Sergio Serafini,Christian Steinkühler,Philip Jones +12 more
TL;DR: 5-Aryl-2-(trifluoroacetyl)thiophenes were identified as a new series of class II HDAC inhibitors (HDACi) and compounds such as 6h, a potent inhibitor of HDAC4 and HDAC6 that displays 40-fold selectivity over HDAC1 and improved stability in HCT116 cancer cells are developed.
References
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