Combinatorial Gene Essentiality and Pharmacological Profiling uncovers enhancer-mediated synthetic lethal interactions with Mediator Kinase [ChIP]

Depletion of CDK8 and its paralogue CDK19, resulted in a global down regulation of mRNA expression, and hence we went to investigate the binding of RNA pol II by ChIP seq at the promoter and at the gene body in the DKO cells. To determine the consequence of loss of CDK8/19 in re-defining enhancers and to underpin the molecular mechanism that providing the preferential BET sensitivity for DKO, we performed ChIP sequencing for MED12, a reminiscent mediator kinase component, BRD4 and H3K27Ac. We identified that MED12 redefines the enhancer landscape in the absence of CDK8/19, recruit BRD4 at the cis regions and can be targeted using BET inhibitors Overall design: Examine the binding of RNA pol II, MED12, H3K27Ac and BRD4 in the genome in the wild type and in CDK8/19 KO cells