The MybMuvB complex is required for YAP dependent transcription of mitotic genes

YAP/TAZ, downstream effectors of the Hippo pathway, are important regulators of proliferation. Here we show that the ability of YAP to activate mitotic gene expression is dependent on the Myb-MuvB (MMB) complex, a master regulator of genes expressed in the G2/M phase of the cell cycle. By carrying out genome-wide expression and binding analyses, we found that YAP promotes binding of the MMB subunit B-MYB to the promoters of mitotic target genes. YAP binds to B-MYB and stimulates B-MYB chromatin-association through distal enhancer elements that interact with MMB-regulated promoters through chromatin looping. The cooperation between YAP and B-MYB is critical for YAP-mediated entry into mitosis. Furthermore, the expression of genes co-activated by YAP and B-MYB is associated with poor survival of cancer patients. Together, our findings provide a molecular mechanism by which YAP and MMB regulate mitotic gene expression and suggest a link between two cancer-relevant signaling pathways. ChIP-seq of LIN9, YAP, B-MYB and histone marks in murine lung adenocarcinoma cells (KPL) and in human MCF10A-YAP5SA cells. Gene expression changes upon Lin9-depletion in KPL cells were measured with RNA-seq.