CBP/p300 and muscle differentiation: no HAT, no muscle

Terminal differentiation of muscle cells follows a precisely orchestrated p rogram of transcriptional regulatory events at the promoters of both muscle -specific and ubiquitous genes. Two distinct families of transcriptional co -activators, GCN5/PCAF and CREB-binding protein (CBP)/p300, are crucial to this process. While both possess histone acetyl-transferase (HAT) activity, previous studies have failed to identify a requirement for CBP/p300 HAT fu nction in myogenic differentiation. We have addressed this issue directly u sing a chemical inhibitor of CBP/p300 in addition to a negative transdomina nt mutant. Our results clearly demonstrate that CBP/p300 HAT activity is cr itical for myogenic terminal differentiation. Furthermore, this requirement is restricted to a subset of events in the differentiation program: cell f usion and specific gene expression. These data help to define the requireme nts for enzymatic function of distinct coactivators at different stages of the muscle cell differentiation program.