Control of the expression of the Mrf4 and Myf5 genes: a BAC transgenic approach.

The muscle-specific transcription factors Mrf4 and Myf5 are two of the four myogenic regulatory factors (MRFs) involved in the transcriptional cascade responsible for skeletal myogenesis in the vertebrate embryo. Myf5 is the first MRF to be expressed in mouse and avian embryos. We have previously described discrete enhancers driving Myf5 expression in epaxial and hypaxial somites, branchial arches and central nervous system, and argued that additional elements are required for proper expression (Summerbell et at., 2000). We have investigated the transcriptional regulation of these two linked genes using bacterial artificial chromosome (BAC) transgenesis. We show that sequences up to 140 kb upstream of Myf5 are involved in the transcription of both genes and that these elements direct expression at different times and anatomical locations through development. In addition, we show that regulation of Mrf4 requires at least four different elements one of which may be shared with Myf5.