The dystrophin promoter is negatively regulated by YY1 in undifferentiated muscle cells.
The dystrophin gene transcription is up-regulated during muscle cell differentiation. Its expression in muscle cells is induced by the binding of the positive regulators serum response factor and dystrophin promoter bending factor (DPBF) on a regulatory CArG element present on the promoter. Here we show that the dystrophin CArG box is also recognized by the zinc finger nuclear factor YY1. Transient transfection experiments show that YY1 negatively regulates dystrophin transcription in C2C12 muscle cells. On the dystrophin CArG element YY1 competes with the structural factor DPBF. We further show that YY1 and DPBF binding to the CArG element induce opposite DNA bends suggesting that their binding induces alternative promoter structures. Along with C2C12 myotube formation YY1 is reduced and we observed that YY1, but not DPBF, is a substrate of m-calpain, a protease that is up-regulated in muscle cell differentiation. Thus, high levels of YY1 in non-differentiated muscle cells down-regulate the dystrophin promoter, at least in part, by interfering with the spatial organization of the promoter.
Galvagni
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F
Dipartimento di Biologia Molecolare, Università di Siena, via Fiorentina 1, 53100 Siena, Italy.
Cartocci
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E
Oliviero
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D001483:Base Sequence; D002154:Calpain / Q000378:metabolism; D002460:Cell Line; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000378:metabolism*; D016189:Dystrophin / Q000235:genetics* / Q000378:metabolism; D050981:Erythroid-Specific DNA-Binding Factors; D005786:Gene Expression Regulation; D006868:Hydrolysis; D009132:Muscles / Q000166:cytology / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D050986:YY1 Transcription Factor
D017931:DNA Primers; D004268:DNA-Binding Proteins; D016189:Dystrophin; D050981:Erythroid-Specific DNA-Binding Factors; D014157:Transcription Factors; D050986:YY1 Transcription Factor; D002154:Calpain