Myf5 is the first myogenic regulatory factor to be expressed in the mouse embryo and it determines the entry of cells into the skeletal muscle programme. A region situated between -58 kb and -48 kb from the gene directs Myf5 transcription at sites where muscles will form. We now show that this region consists of a number of distinct regulatory elements that specifically target sites of myogenesis in the somite, limbs and hypoglossal cord, and also sites of Myf5 transcription in the central nervous system. Deletion of these sequences in the context of the locus shows that elements within the region are essential, and also reveals the combinatorial complexity of the transcriptional regulation of Myf5. Both within the-58 kb to -48 kb region and elsewhere in the locus, multiple sequences are present that direct transcription in subdomains of a single site during development, thus revealing distinct phases of myogenesis when subpopulations of progenitor cells enter the programme of skeletal muscle differentiation.
Analysis of a key regulatory region upstream of the Myf5 gene reveals multiple phases of myogenesis, orchestrated at each site by a combination of elements dispersed throughout the locus
These authors contributed equally to this work
Present address: INSERM U36, Médecine Expérimentale,Collège de France, 11 place Marcelin Berthelot, 75005 Paris Cedex 231,France
Juliette Hadchouel, Jaime J. Carvajal, Philippe Daubas, Lola Bajard, Ted Chang, Didier Rocancourt, David Cox, Dennis Summerbell, Shahragim Tajbakhsh, Peter W. J. Rigby, Margaret Buckingham; Analysis of a key regulatory region upstream of the Myf5 gene reveals multiple phases of myogenesis, orchestrated at each site by a combination of elements dispersed throughout the locus. Development 1 August 2003; 130 (15): 3415–3426. doi: https://doi.org/10.1242/dev.00552
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