The dystrophin promoter is negatively regulated by YY1 in undifferentiatedmuscle cells

The dystrophin gene transcription is up-regulated during muscle cell differ entiation. Its expression in muscle cells is induced by the binding of the positive regulators serum response factor and dystrophin promoter bending f actor (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 nuc lear factor YY1. Transient transfection experiments show that YY1 negativel y regulates dystrophin transcription in C2C12 muscle cells. On the dystroph in CArG element YY1 competes with the structural factor DPBF. We further sh ow that YY1 and DPBF binding to the CArG element induce opposite DNA bends suggesting that their binding induces alternative promoter structures. Alon g 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 i nterfering with the spatial organization of the promoter.