Histone acetyltransferases and deacetylases in the control of cell proliferation and differentiation

Prospects: Histone deacetylase inhibitors

“…The structure of chromatin is complex, madeup of DNA, histones, and non-histone proteins [Luger et al, 1997;Marks et al, 2001;Lehrmann et al, 2002]. The basic repeating unit of chromatin is the nucleosome, composed of approximately 146 bp of DNA wrapped around the histone octamer composed of two copies of each of four histones, H2A, H2B and H3 and H4.…”

“…A recurring theme that emerged from these phylogenetic studies was the common nature of association between HDAC molecules. It is well established that class I and class II HDACs are often found as components of larger transcription factor protein complexes [De Ruijter et al, 2002;Lehrmann et al, 2002;Marks et al, 2004;Sengupta and Seto, 2004;Drummond et al, 2005]. The possible functional significance of association among HDAC molecules is further considered below in the context of studies on the effect of suberoylanilide hydroxamic acid, (SAHA) on proteins associated with the proximal promotor region of the p21 gene [Gui et al, 2004].…”

“…There is abundant evidence that HDACs are not redundant in their biological function [De Ruijter et al, 2002;Lehrmann et al, 2002;Glaser et al, 2003;Verdin et al, 2003;Marks et al, 2004]. HDACs targets include histones and nonhistone proteins which regulate gene expression and proteins involved in regulation of cell cycle progression, and cell death [Lehrmann et al, 2002;Johnstone and Licht, 2003;Warrener et al, 2003;Di Gennaro et al, 2004;Marks et al, 2004;Rosato and Grant, 2004;Drummond et al, 2005].…”

“…HDACs targets include histones and nonhistone proteins which regulate gene expression and proteins involved in regulation of cell cycle progression, and cell death [Lehrmann et al, 2002;Johnstone and Licht, 2003;Warrener et al, 2003;Di Gennaro et al, 2004;Marks et al, 2004;Rosato and Grant, 2004;Drummond et al, 2005]. In addition, acetylation/deacetylation of histone and nonhistone proteins plays an important role in DNA replication and mitosis which does not involve directly altering gene expression.…”

“…HATs, like HDACs, do not bind to DNA directly, but are recruited to multi-protein complexes associated with DNA which differ in their subunit composition [De Ruijter et al, 2002;Lehrmann et al, 2002;Marks et al, 2004;Sengupta and Seto, 2004]. HDACs 1 and 2 are frequently found in complex with Sir3, NURD (nucleosome remodeling and deacetylation), N-Cor (nuclear receptor co-repressor), mSirN3A, Ni-2/NRD, and/or CoREST.…”