Class II histone deacetylases: Structure, function, and regulation

Acetylation of histones, as well as non-histone proteins, plays important r oles in regulating various cellular processes. Dynamic control of protein a cetylation levels in vivo occurs through the opposing actions of histone ac etyltransferases and histone deacetylases (HDACs). In the past few years, d istinct classes of HDACs have been identified in mammalian cells. Class I m embers, such as HDAC1, HDAC2, HDAC3, and HDAC8, are well-known enzymatic tr anscriptional corepressors homologous to yeast Rpd3. Class II members, incl uding HDAC4, HDAC5, HDAC6, HDAC7, and HDAC9, possess domains similar to the deacetylase domain of yeast Hda1. HDAC4, HDAC5, and HDAC7 function as tran scriptional corepressors that interact with the MEF2 transcription factors and the N-CoR, BCoR, and CtBP corepressors. Intriguingly, HDAC4, HDAC5, and probably HDAC7 are regulated through subcellular compartmentalization cont rolled by site-specific phosphorylation and binding of 14-3-3 proteins; the regulation of these HDACs is thus directly linked to cellular signaling ne tworks. Both HDAC6 and HDAC9 possess unique structural modules, so they may have special biological functions. Comprehension of the structure, functio n, and regulation of class II deacetylases is important for elucidating how acetylation regulates functions of histones and other proteins in vivo.