Functional characterization of an amino-terminal region of HDAC4 that possesses MEF2 binding and transcriptional repressive activity.
Like the full-length histone deacetylase (HDAC) 4, its amino terminus (amino acids 1-208) without the carboxyl deacetylase domain is also known to effectively bind and repress myocyte enhancer factor 2 (MEF2). Within this repressive amino terminus, we further show that a stretch of 90 amino acids (119-208) displays MEF2 binding and repressive activity. The same region is also found to associate specifically with HDAC1 which is responsible for the repressive effect. The amino terminus of HDAC4 can associate with the DNA-bound MEF2 in vitro, suggesting that it does not repress MEF2 simply by disrupting the ability of MEF2 to bind DNA. In vivo, MEF2 induces nuclear translocation of both the full-length HDAC4 and HDAC4-(1-208), whereas the nuclear HDAC4 as well as HDAC4-(1-208) in turn specifically sequesters MEF2 to distinct nuclear bodies. In addition, we show that MyoD and HDAC4 functionally antagonize each other to regulate MEF2 activity. Combined with data from others, our data suggest that the full-length HDAC4 can repress MEF2 through multiple independent repressive domains.
Chan
Jonathan K L
JK
Department of Biochemistry, Hong Kong University of Science & Technology, Hong Kong, China.
Sun
Luguo
L
Yang
Xiang-Jiao
XJ
Zhu
Guang
G
Wu
Zhenguo
Z
D021581:Active Transport, Cell Nucleus; D000595:Amino Acid Sequence; D000818:Animals; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D049452:Green Fluorescent Proteins; D006655:Histone Deacetylases / Q000737:chemistry* / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D008164:Luminescent Proteins; D064326:MEF2 Transcription Factors; D008856:Microscopy, Fluorescence; D017570:MyoD Protein / Q000037:antagonists & inhibitors / Q000502:physiology; D018006:Myogenic Regulatory Factors; D017434:Protein Structure, Tertiary; D012097:Repressor Proteins / Q000737:chemistry* / Q000378:metabolism* / Q000502:physiology; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014158:Transcription, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; D008164:Luminescent Proteins; D064326:MEF2 Transcription Factors; D017570:MyoD Protein; D018006:Myogenic Regulatory Factors; D012097:Repressor Proteins; D014157:Transcription Factors; D049452:Green Fluorescent Proteins; C400300:HDAC4 protein, human; D006655:Histone Deacetylases