BRPF1 co-occupies with H3K4me3 and H3K23ac in human ESCs essential to pluripotency [ChIP-seq]

Post-translational modifications (PTMs) on histones play essential roles in cell fate decisions during development. However, how these PTMs are recognized and coordinated remains to be fully illuminated. Here, we show that BRPF1, a multi-histone binding module protein, is essential to maintain pluripotency in human embryonic stem cells (ESCs). BRPF1, H3K4me3 and H3K23ac substantially co-occupy the active and stemness genes in hESCs. BRPF1 deletion impairs H3K23ac and leads to pluripotency exit and closed chromatin accessibility on stemness genes. Deletion of the N terminal or PHD-zinc knuckle-PHD (PZP) modules completely impairs BRPF1 to maintain hESC pluripotency while PWWP module deletion only partially impact its functions. Together, we reveal that the multi-histone binding module protein, BRPF1 co-ordinates the crosstalk between different histone modifications to maintain the pluripotency in hESCs. We performed the ChIP-Seq assay to study FLAG(BRPF1), H3K4me3 and H3K27me3 location of the triple-FLAG knock-in(KI) into BRPF1 locus in hESCs. In addition, we studied H3K4me3 binding of BRPF1knock-out (D12) in hESCs