Regulation Of TAZ (WWTR1) By Protein-Protein Interactions In Striated Muscle

Abstract

Tissue growth depends on cellular proliferation, survival, and differentiation. Hippo signaling controls these processes by regulating transcriptional co-activators Yap/Taz. Taz function is context-dependent, including repression of myogenic differentiation. Taz does not bind DNA; its activity is determined by interacting partners. To discover functional regulators of Taz, nuclear FLAG-affinity purification and LC-MS/MS were performed in HEK293T, identifying 57 interactors (33 unique; 24 ³3-fold enriched). Among these, transcription factor Yin-Yang1 (YY1) was prioritized. Biochemical analyses revealed YY1 binds Taz at/near its Tead-binding domain, with Tead1 enhancing this interaction. YY1 repressed Taz-mediated transcription on a Tead-responsive reporter. In proliferating myoblasts, YY1 increased phospho-Taz (Ser89), its Hippo-inactivated form. Taz formed LLPS-driven nuclear condensates, during which YY1 was excluded from the nucleus. During differentiation, YY1-mediated stabilization of phospho-Taz (Ser89) was not observed, and Taz and YY1 co-operatively repressed myogenic gene expression. Collectively, these findings identify YY1 as a regulator of Taz function in striated muscle.