Displacement of BrdUrd-induced YY1 by serum response factor activates skeletal alpha-actin transcription in embryonic myoblasts.
Muscle-restricted transcription of the skeletal alpha-actin gene is controlled in part by a positive regulator, serum response factor (SRF), and a negative regulator, F-ACT1, which bind competitively to the most proximal serum response element (SRE1). We show here that F-ACT1 is identical to a transcription factor recently cloned and described as YY1, NF-E1, delta, or UCRBP. We found that although the DNA-binding activity of SRF accumulates during myogenesis, that of YY1 diminishes simultaneously. Myoblasts rendered incapable of differentiation by BrdUrd treatment exhibited the highest level of YY1 and the lowest level of SRF activities. Transfected SRF could directly transactivate the skeletal alpha-actin promoter by overcoming the inhibitory effect of BrdUrd-induced YY1. The transactivation depends on intact SRE DNA elements and requires the DNA-binding/dimerization domain of SRF as well as its C-terminal half rich in serines and threonines. Since the functions of YY1 and SRF appear to be developmentally regulated, the convergence of their binding sites upon the SRE constitutes an integrated mechanism whereby temporal and spatial muscle gene expression may be accomplished.
Lee
T C
TC
Department of Cell Biology, Baylor College of Medicine, Houston, TX 77030.
Shi
Y
Y
Schwartz
R J
RJ
D000199:Actins / Q000235:genetics*; D000818:Animals; D001973:Bromodeoxyuridine / Q000494:pharmacology; D002478:Cells, Cultured; D002642:Chick Embryo; D016384:Consensus Sequence; D004268:DNA-Binding Proteins / Q000378:metabolism* / Q000494:pharmacology*; D050981:Erythroid-Specific DNA-Binding Factors; D005786:Gene Expression Regulation / Q000187:drug effects; D066298:In Vitro Techniques; D009132:Muscles / Q000502:physiology*; D009687:Nuclear Proteins / Q000494:pharmacology*; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D012045:Regulatory Sequences, Nucleic Acid; D012097:Repressor Proteins / Q000378:metabolism*; D026362:Serum Response Factor; D014157:Transcription Factors; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014162:Transfection; D050986:YY1 Transcription Factor
D000199:Actins; D004268:DNA-Binding Proteins; D050981:Erythroid-Specific DNA-Binding Factors; D009687:Nuclear Proteins; D012333:RNA, Messenger; D012097:Repressor Proteins; D026362:Serum Response Factor; D014157:Transcription Factors; D050986:YY1 Transcription Factor; D001973:Bromodeoxyuridine