Yin Yang 1 represses alpha-myosin heavy chain gene expression in pathologic cardiac hypertrophy.
In the work presented here, we elucidate a mechanism for the repression of alpha-myosin heavy chain (MyHC) during pathological cardiac hypertrophy. We demonstrate that the transcription factor Yin Yang 1 (YY1) significantly decreases endogenous alpha-MyHC mRNA and protein expression in neonatal rat ventricular myocytes. Furthermore, mutation of the YY1 binding sites in the proximal rat alpha-MyHC promoter increases promoter activity and alleviates YY1-mediated repression of the promoter. Despite the presence of 5 sites that bind YY1, only one site, located at -94bp of the rat alpha-MyHC promoter, is both necessary and sufficient for pathological repression of the promoter by phorbol esters, revealing a unique mechanism for the repression of alpha-MyHC expression during cardiac hypertrophy.
Mariner
Peter D
PD
Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, CO 80309, USA.
Luckey
Stephen W
SW
Long
Carlin S
CS
Sucharov
Carmen C
CC
Leinwand
Leslie A
LA
D000818:Animals; D000831:Animals, Newborn; D006332:Cardiomegaly / Q000378:metabolism*; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D050981:Erythroid-Specific DNA-Binding Factors; D005786:Gene Expression Regulation; D006352:Heart Ventricles / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000378:metabolism*; D018995:Myosin Heavy Chains / Q000378:metabolism*; D051381:Rats; D011994:Recombinant Proteins / Q000378:metabolism; D013329:Structure-Activity Relationship; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D024723:Ventricular Myosins / Q000235:genetics / Q000378:metabolism*; D050986:YY1 Transcription Factor
D004268:DNA-Binding Proteins; D050981:Erythroid-Specific DNA-Binding Factors; D011994:Recombinant Proteins; D014157:Transcription Factors; D050986:YY1 Transcription Factor; C494700:Yy1 protein, rat; D024723:Ventricular Myosins; D018995:Myosin Heavy Chains