Bifunctional transcriptional properties of YY1 in regulating muscle actin and c-myc gene expression during myogenesis.
Oncogene expression is generally incompatible with terminal cell differentiation as in myogenesis. We present evidence that this incompatibility can be caused in part by the dual activity of a Kruppel-related zinc finger, YY1 (formerly F-ACT1), in differentially regulating oncogene and muscle-specific gene expression. The c-myc and skeletal alpha-actin gene promoters contain YY1 binding sites thought to act either as positive or negative cis-acting elements. Through manipulating the intracellular level of YY1 by treating primary myoblasts with bromodeoxyuridine (BrdU), which inhibited myogenesis and increased the YY1 protein content, or by transfecting YY1 cDNA expression vector, we show that it can simultaneously inhibit and activate expression of the skeletal alpha-actin and c-myc genes, respectively. The transrepression activity of YY1 solely depends on its C-terminal zinc finger region (amino acids 297-407) while its transactivation function requires an additional N-terminal domain (amino acids 1-90) normally masked in the full-length protein. We propose that the high level of YY1 in proliferating myoblasts might serve to maintain c-myc expression and suppress muscle actin expression, which can then be gradually reversed by downregulating YY1 activity toward myogenesis.
Lee
T C
TC
Department of Cell Biology, Baylor College of Medicine, Houston, Texas 77030.
Zhang
Y
Y
Schwartz
R J
RJ
D000199:Actins / Q000378:metabolism*; D000818:Animals; D002454:Cell Differentiation; D002455:Cell Division; D002478:Cells, Cultured; D002642:Chick Embryo; D004268:DNA-Binding Proteins / Q000494:pharmacology*; D050981:Erythroid-Specific DNA-Binding Factors; D005786:Gene Expression Regulation; D016259:Genes, myc; D009132:Muscles / Q000196:embryology*; D009154:Mutation; D012097:Repressor Proteins; D015534:Trans-Activators; D014157:Transcription Factors / Q000494:pharmacology*; D015533:Transcriptional Activation; D050986:YY1 Transcription Factor; D016335:Zinc Fingers
D000199:Actins; D004268:DNA-Binding Proteins; D050981:Erythroid-Specific DNA-Binding Factors; D012097:Repressor Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D050986:YY1 Transcription Factor