Jumonji represses alpha-cardiac myosin heavy chain expression via inhibiting MEF2 activity.
Expression of alpha-cardiac myosin heavy chain gene (alphaMHC) is developmentally regulated in normal embryonic hearts and down-regulated in cardiac myopathy and failing hearts. Jumonji (JMJ) has been shown to be critical for normal cardiovascular development and functions as a transcriptional repressor. Here, we demonstrate that JMJ represses alphaMHC expression through inhibition of myocyte enhancer factor 2 (MEF2) activity. In primary cardiomyocytes, overexpression of JMJ leads to marked reduction of endogenous alphaMHC expression. JMJ represses the synergistic activation of alphaMHC by MEF2 and thyroid hormone receptor (TR). Interestingly, JMJ inhibits transcriptional activities of all MEF2 isoforms, but not the TR-dependent activation. The transcriptional repression domain of JMJ interacts with the N-terminal part of MEF2A, resulting in the repression of MEF2A activities. These results suggest that JMJ represses alphaMHC expression via protein-protein interaction with MEF2A.
Kim
Tae-gyun
TG
Department of Anatomy and Cardiovascular Research Center, University of Wisconsin Medical School, Madison, WI 53706, USA.
Jung
Jooyoung
J
Mysliwiec
Matthew R
MR
Kang
Seogyoun
S
Lee
Youngsook
Y
D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D064326:MEF2 Transcription Factors; D051379:Mice; D032383:Myocytes, Cardiac / Q000378:metabolism*; D018006:Myogenic Regulatory Factors; D018995:Myosin Heavy Chains / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D063151:Polycomb Repressive Complex 2; D051381:Rats; D011994:Recombinant Proteins / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*
D004268:DNA-Binding Proteins; C093650:Jarid2 protein, mouse; D064326:MEF2 Transcription Factors; C578036:Mef2a protein, mouse; D018006:Myogenic Regulatory Factors; D009419:Nerve Tissue Proteins; D011994:Recombinant Proteins; D014157:Transcription Factors; D063151:Polycomb Repressive Complex 2; D018995:Myosin Heavy Chains