HDAC4, a human histone deacetylase related to yeast HDA1, is a transcriptional corepressor.
Histone acetylation plays an important role in regulating chromatin structure and thus gene expression. Here we describe the functional characterization of HDAC4, a human histone deacetylase whose C-terminal part displays significant sequence similarity to the deacetylase domain of yeast HDA1. HDAC4 is expressed in various adult human tissues, and its gene is located at chromosome band 2q37. HDAC4 possesses histone deacetylase activity intrinsic to its C-terminal domain. When tethered to a promoter, HDAC4 represses transcription through two independent repression domains, with repression domain 1 consisting of the N-terminal 208 residues and repression domain 2 containing the deacetylase domain. Through a small region located at its N-terminal domain, HDAC4 interacts with the MADS-box transcription factor MEF2C. Furthermore, HDAC4 and MEF2C individually upregulate but together downmodulate c-jun promoter activity. These results suggest that HDAC4 interacts with transcription factors such as MEF2C to negatively regulate gene expression.
Wang
A H
AH
Molecular Oncology Group, Department of Medicine, McGill University, Montreal, Quebec, Canada.
Bertos
N R
NR
Vezmar
M
M
Pelletier
N
N
Crosato
M
M
Heng
H H
HH
Th'ng
J
J
Han
J
J
Yang
X J
XJ
D000595:Amino Acid Sequence; D002874:Chromosome Mapping; D002889:Chromosomes, Human, Pair 2; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins / Q000378:metabolism; D005786:Gene Expression Regulation; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D026161:MADS Domain Proteins; D064326:MEF2 Transcription Factors; D008969:Molecular Sequence Data; D005810:Multigene Family; D018006:Myogenic Regulatory Factors; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D014018:Tissue Distribution; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic
D004268:DNA-Binding Proteins; D026161:MADS Domain Proteins; D064326:MEF2 Transcription Factors; C578040:MEF2C protein, human; D018006:Myogenic Regulatory Factors; D016755:Proto-Oncogene Proteins c-jun; D012097:Repressor Proteins; D014157:Transcription Factors; C400300:HDAC4 protein, human; D006655:Histone Deacetylases