TY - JOUR T1 - Interaction of YAP with the Myb-MuvB (MMB) complex defines a transcriptional program to promote the proliferation of cardiomyocytes JF - bioRxiv DO - 10.1101/824755 SP - 824755 AU - Marco Gründl AU - Susanne Walz AU - Laura Hauf AU - Melissa Schwab AU - Kerstin Marcela Werner AU - Susanne Spahr AU - Carsten P. Ade AU - Stefan Gaubatz Y1 - 2019/01/01 UR - http://biorxiv.org/content/early/2019/10/30/824755.abstract N2 - YAP, a major downstream effector of the Hippo signaling pathway, is an important regulator of cell proliferation. The ability of YAP to regulate G2/M gene expression is dependent on the Myb-MuvB (MMB) complex, consisting of the evolutionary MuvB core complex and the facultative B-MYB subunit, a transcription factor. Here we show that YAP directly binds to B-MYB. Disruption of the YAP/B-MYB interaction by overexpression of the YAP binding domain of B-MYB results in errors in cell division. We also show that YAP and MMB interact in vivo in the developing heart. Genome studies revealed that YAP and MMB regulate an overlapping set of cell cycle genes in cardiomyocytes. Cardiac specific deletion of the LIN9 subunit of MMB prevents the upregulation of cell cycle genes and the increased proliferation of cardiomyocytes lacking the Hippo-signaling component SAV1. Similarly, we find that proliferation of postnatal cardiomyocytes induced by constitutive active YAP depends on MMB. Our findings provide new insights in the YAP induced proliferation of cardiomyocytes through the functional interaction with MMB. ER -