FUNCTIONAL COOPERATION OF SOX6 AND NFIX REGULATES FIBER TYPE SPECIFICATION DURING PRE-NATAL MUSCLE DEVELOPMENT

Nuclear factor I X (Nfix) is a key regulator of fetal myogenesis acting both as an activator of fetal-specific genes and as a repressor of embryonic muscle genes, such as MyHC-I. Here we show that Sox6, belonging to the Sox factors family, cooperates with Nfix in fetal muscle to repress MyHC-I at the transcriptional level. Sox6 and Nfix are co-expressed in fetal myoblasts and co-immunoprecipitate in muscle cells. By ChIP assay, we show that Nfix is required for Sox6 binding to the MyHC-I promoter in fetal myoblasts and thus for Sox6 repressive activity. Moreover, we show that Sox6 is a direct activator of MyHC-I in embryonic muscle and is required for proper Nfix function in fetal muscle. These data demonstrate functional cooperation of Sox6 and Nfix in the regulation of embryonic muscle genes, that is evolutionary conserved in mouse and zebrafish.