GSE113714
ChIP-Seq of H4K5acK8ac and BRD2 in H23 NSCLC cell line treated with 500 nM JQ1 for 24h
Changes in acetylation of histone H4 are a common hallmark of cancer cells. In leukemia cells, histone H4 is characterized by loss of K16 mono-acetylation. Bromodomain proteins specifically recognize acetylated lysines and have been used as a target for anti cancer drug, JQ1 and iBET. Although acetylation and de-acetylation of histone H4 have been shown to have big impact in cancer cells, little attention has been focused on histone H4-acetylation at a genome level. To uncover potential epigenetic role of hyper-acetylated histone H4 at a genome-wide level in cancer cell, we generated a novel monoclonal antibody specifically recognizing histone H4 with at least two acetylated lysine residues (H4K5ac+K8ac).  At the genome-wide level, hyper-acetylated histone H4 is associated with promoter and regulatory element (active enhancer, eRNA and super enhancer). We show that diacetylation at K5 and K8 of histone H4 co-localizes H3K27ac and BRD2 in the majority of active enhancer and promoters. However BRD2 has a stronger association with H4K5acK8ac. Furthermore we identified two specific chromatin states, which separately contain either H3K27ac or acetylated histone H4.  Although JQ1 led to global reduction of BRD2 binding on the chromatin, only local changes of histone H4 multi-acetylation were observed upon BET inhibition by JQ1 Overall design: ChIP-Seq of H4K5acK8ac and BRD2 in H23 NSCLC cell line treated with 500 nM JQ1 for 24h