The role of p300 in regulation of Myf5 expression

Abstract

The commitment of cells to skeletal muscle differentiation is regulated by the myogenic regulatory factors Myf5, MyoD, myogenin and MRF4. Myf5 is the earliest of the MRFs expressed in an embryo. An array of transcriptional factors and signals present in dermomyotome and myotome such as Wnt, Shh, Six1/4, Eya1/2 and Pax3/7 regulate the expression of Myf5. Also, the HAT activity of coactivator p300 is also needed for Myf5 expression. However, the exact function of the p300 HAT activity that is required for expression of Myf5 has not been determined. The spatio-temporal expression of Myf5 is also regulated by a large number of enhancers spread over 140 kb upstream of the transcription start site. The early epaxial enhancer regulates the expression at the earliest time point known. We hypothesized that HAT activity of p300 may be involved in direct regulation of Myf5. We used the embryonal carcinoma P19 cells to study skeletal myogenesis and the chemical inhibitor curcumin to study the role ofp300 HAT activity. Curcumin was able to inhibit commitment into skeletal myogenesis by downregulating expression of Myf5 and MyoD. Furthermore we show that p300 is present at the early epaxial ehancer and that the function ofp300 there may be histone acetylation. Therefore we provide evidence that p300 may be directly involved in regulation of Myf5 expression.