Oral Presentation 16th Asian Conference on Transcription 2019

Vgll4 functions as transcription co-repressor or co-activator at different stage of myogenesis (1179)

Xue Feng 1 , Fei Wang 1 , Lei Zhang 1 , Ping Hu 1
  1. Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai, SHANGHAI, China

VGLL4 is originally identified as a negative regulator of YAP-dependent gene transcription. Here we show that VGLL4 regulates muscle regeneration in both YAP-dependent and YAP-independent manners at different stages. Vgll4 also serves as either a co-repressor or co-activator depending on whether YAP is involved. We find that knockout of VGLL4 leads to smaller myofiber size and defective muscle contraction force. What’s more, our studies reveal that knockout of VGLL4 results in increased muscle satellite cell proliferation and impaired myoblast differentiation, ultimately leading to delayed muscle regeneration. Mechanistically, our results show that VGLL4 works as a conventional YAP inhibitor at the proliferation stage of muscle regeneration. At the differentiation stage, VGLL4 acts as a co-activator of TEAD4 to promote MyoG transactivation and facilitate the initiation of differentiation in a YAP-independent manner. Moreover, VGLL4 stabilizes the protein-protein interaction between MyoD and TEAD4 to achieve efficient MyoG transactivation. Our findings define the dual roles of VGLL4 in regulating muscle regeneration at different stages, and may open novel therapeutic perspectives for muscle regeneration.