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.
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Review Article|
March 15 2003
Histone deacetylases (HDACs): characterization of the classical HDAC family
Annemieke J.M. de RUIJTER;
Annemieke J.M. de RUIJTER
Academic Medical Centre, University of Amsterdam, Laboratory Genetic Metabolic Diseases, Department of Paediatrics/Emma Children's Hospital and Clinical Chemistry, P.O. Box 22700, 1100 DE Amsterdam, The Netherlands
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Albert H. van GENNIP;
Albert H. van GENNIP
Academic Medical Centre, University of Amsterdam, Laboratory Genetic Metabolic Diseases, Department of Paediatrics/Emma Children's Hospital and Clinical Chemistry, P.O. Box 22700, 1100 DE Amsterdam, The Netherlands
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Huib N. CARON;
Huib N. CARON
Academic Medical Centre, University of Amsterdam, Laboratory Genetic Metabolic Diseases, Department of Paediatrics/Emma Children's Hospital and Clinical Chemistry, P.O. Box 22700, 1100 DE Amsterdam, The Netherlands
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Stephan KEMP;
Stephan KEMP
Academic Medical Centre, University of Amsterdam, Laboratory Genetic Metabolic Diseases, Department of Paediatrics/Emma Children's Hospital and Clinical Chemistry, P.O. Box 22700, 1100 DE Amsterdam, The Netherlands
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André B.P. van KUILENBURG
André B.P. van KUILENBURG
1
Academic Medical Centre, University of Amsterdam, Laboratory Genetic Metabolic Diseases, Department of Paediatrics/Emma Children's Hospital and Clinical Chemistry, P.O. Box 22700, 1100 DE Amsterdam, The Netherlands
1To whom correspondence should be addressed: Academic Medical Centre, Lab. Genetic Metabolic Diseases, F0-224, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands (e-mail a.b.vankuilenburg@amc.uva.nl).
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Publisher: Portland Press Ltd
Received:
August 21 2002
Revision Received:
October 30 2002
Accepted:
November 12 2002
Accepted Manuscript online:
March 15 2003
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London ©2003
2003
Biochem J (2003) 370 (3): 737–749.
Article history
Received:
August 21 2002
Revision Received:
October 30 2002
Accepted:
November 12 2002
Accepted Manuscript online:
March 15 2003
Citation
Annemieke J.M. de RUIJTER, Albert H. van GENNIP, Huib N. CARON, Stephan KEMP, André B.P. van KUILENBURG; Histone deacetylases (HDACs): characterization of the classical HDAC family. Biochem J 15 March 2003; 370 (3): 737–749. doi: https://doi.org/10.1042/bj20021321
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