Members of the TEAD family of transcription factors regulate the expression of Myf5 in ventral somitic compartments

Abstract

The transcriptional regulation of the Mrf4/Myf5 locus depends on a multitude of enhancers that, in equilibria with transcription balancing sequences and the promoters, regulate the expression of the two genes throughout embryonic development and in the adult. Transcription in a particular set of muscle progenitors can be driven by the combined outputs of several enhancers that are not able to recapitulate the entire expression pattern in isolation, or by the action of a single enhancer the activity of which in isolation is equivalent to that within the context of the locus. We identified a new enhancer element of this second class, ECR111, which is highly conserved in all vertebrate species and is necessary and sufficient to drive Myf5 expression in ventro-caudal and ventro-rostral somitic compartments in the mouse embryo. EMSA analyses and data obtained from binding-site mutations in transgenic embryos show that a binding site for a TEA Domain (TEAD) transcription factor is essential for the function of this new enhancer, while ChIP assays show that at least two members of the family of transcription factors bind to it in vivo.

Highlights

► The ECR111 enhancer controls Myf5 expression in ventral somitic compartments in early development. ► A TEAD binding site is essential for the activity of the ECR111 enhancer. ► ChIP analyses show that TEAD factors bind in vivo to the ECR111 enhancer. ► TEAD proteins localise to the myotome and the dermomyotome during early development.