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Global transcriptional regulation of the Mrf4/Myf5 locus

AutorLópez-Mayorga, Macarena ; Giráldez-Pérez, Rosa María; Carvajal, Jaime J.
Fecha de publicación2013
Citación2nd SPBD Meeting (2013)
ResumenMyogenic Regulatory Factors are a family of transcription factors essential for the determination, specification and differentiation of skeletal muscle during embryonic development. Two members of this family, Mrf4 and Myf5, are closely linked in all vertebrates analysed. We have studied the transcriptional regulation of Mrf4 and Myf5 extensively in transgenic mice and shown that a multitude of interdigitated enhancers regulate gene activation at different times and anatomical locations. Despite this complex architecture the enhancers are able to recognize their respective core promoters, and we have shown that a series of equilibria-states between transcription balancing sequences (trabs), promoters and the enhancers present in the locus is active in order to drive correct expression and transcriptional initiation. The proposed model is well supported by the cis-effects seen in the different knock out Mrf4 and Myf5 alleles created independently. We are investigating the nature of this new class of transcription element by standard cell culture and transgenic approaches. We are testing the hypothesis of the equilibria states by using chromosomal conformation capture (4C-seq) techniques on mouse embryos at different developmental stages. In addition, we are using the muscle cell line C2C12 (differentiated and undifferentiated) to identify nuclear matrix attachment regions within the locus and the possible changes in structure that it may experiment as differentiation takes place. The integration of the data sets obtained by these complementary approaches should provide a clear view of the contribution of trabs towards the global regulation of the locus as well as unveil other elements that may be involved in the global regulation.
DescripciónResumen del póster presentado al 2nd Meeting of the Portuguese Society for Developmental Biology, celebrado en Lisboa (Portugal) del 24 al 26 de octubre de 2013.-- et al.
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