Effect of cortistatin A (CA) on enhancer occupancy in CA-sensitive and -insensitive human cell lines

We characterized the marine natural product cortistatin A (CA) as an inhibitor of CDK8 to determine whether pharmacologic inhibition of CDK8 regulates super-enhancer function and inhibits AML proliferation. In this series, we use ChIP-seq of H3K27ac, H3K4me1, MED1, CDK8, BRD4, and RNA polymerase II (PolII) to examine enhancer occupancy and transcriptional response to CA in human cells lines. ChIP-seq was carried out in CA-sensitive: MOLM-14 cells (H3K27Ac, H3K4me1, MED1, CDK8, BRD4, and PolII), MV4;11(H3K27Ac, CDK8), SET2 (H3K27Ac, CDK8), and in CA-insensitive cells: K562 (CDK8).