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
Reads0
Chats0
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
More filters
Journal ArticleDOI
Epigenetic mechanisms in stroke and epilepsy.
TL;DR: Profiling the array of genes that are epigenetically dysregulated in response to neuronal insults is likely to advance the understanding of the mechanisms underlying the pathophysiology of these disorders and may lead to the identification of novel therapeutic strategies for the amelioration of these serious human conditions.
Journal ArticleDOI
Epigenetic changes and disturbed neural development in a human embryonic stem cell-based model relating to the fetal valproate syndrome
Nina V. Balmer,Matthias K. Weng,Bastian Zimmer,Violeta N. Ivanova,Stuart M. Chambers,Elena Nikolaeva,Smita Jagtap,Agapios Sachinidis,Jürgen Hescheler,Tanja Waldmann,Marcel Leist +10 more
TL;DR: Human embryonic stem cells are used as a model to investigate the modes of action of VPA and changes in the methylation of lysines 4 and 27 of histone H3 were detected in the promoter region of PAX6 and OCT4, providing a more general mechanistic rational for the regulation of developmentally important genes at non-cytotoxic drug concentrations.
Journal ArticleDOI
Epigenetic regulation of Smad2 and Smad3 by profilin-2 promotes lung cancer growth and metastasis.
TL;DR: It is shown that profilin-2 (Pfn2) increases Smad2 and Smad3 expression via an epigenetic mechanism, and that profilsad expression correlate with an unfavourable prognosis of lung cancer patients, suggesting a potential molecular target for the development of anticancer drugs.
Journal ArticleDOI
Histone deacetylase 2 (HDAC2) regulates chromosome segregation and kinetochore function via H4K16 deacetylation during oocyte maturation in mouse.
Pengpeng Ma,Richard M. Schultz +1 more
TL;DR: Hdac2 is implicate as the major HDAC that regulates global histone acetylation during oocyte development and HDAC2 is largely responsible for the deacetylation of H4K16 during maturation, and the results provide additional support that histone deacetyation that occurs during oocytes maturation is critical for proper chromosome segregation.
Journal ArticleDOI
Epigenetic events in malignant melanoma.
TL;DR: To date at least 50 genes have been reported to be dysregulated in melanoma by aberrant DNA methylation and accumulating evidence suggests that mistargetting of histone modifications and altered chromatin remodeling activities will play a key role in melanomas.
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.