Histone H3K4me1 and H3K27ac play roles in nucleosome depletion and eRNA transcription, respectively, at enhancers

ABSTRACT Histone H3K4me1 and H3K27ac are enhancer specific modifications and are required for enhancers to activate transcription of target genes. However the reciprocal effects of these histone modifications on each other and their roles in enhancers are not clear. Here to comparatively analyze the role of these modifications, we inhibited H3K4me1 and H3K27ac by deleting SET domain of histone methyltransferases MLL3 and MLL4 and HAT domain of histone acetyltransferase p300, respectively, in erythroid K562 cells. The loss of H3K4me1 reduced H3K27ac at the β-globin enhancer LCR HSs, but H3K27ac reduction did not affect H3K4me1. This unequal relationship between two modifications was revealed in putative enhancers by genome-wide analysis using ChIP-seq. Histone H3 depletion at putative enhancers was weakened by the loss of H3K4me1 but not by the loss of H3K27ac. Chromatin remodeling complexes were recruited into the β-globin LCR HSs in a H3K4me1-dependent manner. In contrast, H3K27ac was required for enhancer RNA (eRNA) transcription, and H3K4me1 was not enough for it. Forced H3K27ac induced eRNA transcription without affecting H3K4me1 at the β-globin LCR HSs. These results indicate that H3K4me1 and H3K27ac affect each other in different ways and play more direct roles in nucleosome depletion and eRNA transcription, respectively, at enhancers.