Vestigial‐like 3 regulates myosin light chain and skeletal α‐actin promoters

Drosophila Vestigial (Vg) interacts with Scalloped protein to potentiate the indirect flight muscles development. Recently, one of the four mammalian Vg homologs, Vestigial‐like‐3 (Vgl‐3), was found to be associated with the myogenic lineage during mouse embryonic development. However, the function of Vgl‐3 is not known. Here, we characterized Vgl‐3 as a cofactor that regulates muscle‐specific promoters. Mouse multi‐tissue Northern blot showed two transcripts at 1.5 kb in the lung and 3.2 kb in the heart. During muscle differentiation, Vgl‐3 mRNA level remained constant but its protein level decreased. Like Vgl‐2, Vgl‐3 also interacted with MEF2, TEAD1 and TEAD4 muscle‐specific transcription factors in mammalian two‐hybrid assays. Functionally, the co‐expression of Vgl‐3 and MEF2 co‐activates an MEF2‐dependent promoter. Vgl‐3, however, repressed the mouse skeletal α‐actin (ACTA1) promoter activity by 5‐fold. To identify novel Vgl‐3 interactors, we exploited a bioinformatic approach and discovered Ying Yang 1 (YY1) as a plausible candidate. Immunoprecipitation revealed a physical interaction between Vgl‐3 and the ACTA1 repressor, YY1. Taken together, Vgl‐3 is a transcription cofactor that may have a role in regulating a series of muscle‐specific promoters by interacting not only with TEAD and MEF2 transcription factors but also with the multifunctional YY1 protein. (Supported by NSERC)