RT Journal Article
SR Electronic
T1 Interaction of YAP with the Myb-MuvB (MMB) complex defines a transcriptional program to promote the proliferation of cardiomyocytes
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 824755
DO 10.1101/824755
A1 Marco Gründl
A1 Susanne Walz
A1 Laura Hauf
A1 Melissa Schwab
A1 Kerstin Marcela Werner
A1 Susanne Spahr
A1 Carsten P. Ade
A1 Stefan Gaubatz
YR 2019
UL http://biorxiv.org/content/early/2019/10/30/824755.abstract
AB 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.