Interdependent genomic binding of BAP1 and MLL4 regulates a subset of gene expression in HCT116

Our genomic studies show that ~20% of MLL4 chromatin binding sites overlap with BAP1 binding regions in HCT116 human colon cancer cells. By comparing MLL4 and BAP1 localization in wild type and knockout cells, we show an interdependent genomic binding of MLL4 and BAP1 on MLL4+ BAP1+ enhancers. Profiling of transcriptomes reveals that a small subset of gene expression is co-regulated by MLL4 and BAP1. Together, our findings identify a functional interaction between enhancer H3K4 methyltransferase MLL4 and H2A deubiquitinase. Overall design: Expression profiling by RNA-Seq in WT, MLL4 KO and BAP1 KO HCT116, and ChIP-Seq profiling of MLL4, BAP1-T7 and H3K4me1