Class II histone deacetylases: structure, function, and regulation.
Acetylation of histones, as well as non-histone proteins, plays important roles in regulating various cellular processes. Dynamic control of protein acetylation levels in vivo occurs through the opposing actions of histone acetyltransferases and histone deacetylases (HDACs). In the past few years, distinct classes of HDACs have been identified in mammalian cells. Class I members, such as HDAC1, HDAC2, HDAC3, and HDAC8, are well-known enzymatic transcriptional corepressors homologous to yeast Rpd3. Class II members, including HDAC4, HDAC5, HDAC6, HDAC7, and HDAC9, possess domains similar to the deacetylase domain of yeast Hdal. HDAC4, HDAC5, and HDAC7 function as transcriptional 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 controlled by site-specific phosphorylation and binding of 14-3-3 proteins; the regulation of these HDACs is thus directly linked to cellular signaling networks. Both HDAC6 and HDAC9 possess unique structural modules, so they may have special biological functions. Comprehension of the structure, function, and regulation of class II deacetylases is important for elucidating how acetylation regulates functions of histones and other proteins in vivo.
Bertos
N R
NR
Department of Medicine, McGill University Health Centre, Montreal, QC, Canada.
Wang
A H
AH
Yang
X J
XJ
D048948:14-3-3 Proteins; D000107:Acetylation; D021581:Active Transport, Cell Nucleus; D000429:Alcohol Oxidoreductases; D000595:Amino Acid Sequence; D000818:Animals; D004268:DNA-Binding Proteins / Q000378:metabolism; D006655:Histone Deacetylases / Q000737:chemistry* / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D006801:Humans; D064326:MEF2 Transcription Factors; D008954:Models, Biological; D008969:Molecular Sequence Data; D018006:Myogenic Regulatory Factors; D009687:Nuclear Proteins / Q000378:metabolism; D056971:Nuclear Receptor Co-Repressor 1; D010750:Phosphoproteins / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism; D016415:Sequence Alignment; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D016335:Zinc Fingers / Q000235:genetics
D048948:14-3-3 Proteins; D004268:DNA-Binding Proteins; D006657:Histones; D064326:MEF2 Transcription Factors; D018006:Myogenic Regulatory Factors; C539127:NCOR1 protein, human; D009687:Nuclear Proteins; D056971:Nuclear Receptor Co-Repressor 1; D010750:Phosphoproteins; D012097:Repressor Proteins; D014157:Transcription Factors; D000429:Alcohol Oxidoreductases; C096794:C-terminal binding protein; D014446:Tyrosine 3-Monooxygenase; D006655:Histone Deacetylases