Genome-wide Analysis of Histone Modifications Reveals Dynamic Associations between Bivalent Promoter and Enhancer

In embryonic stem cells, many promoters harbor a distinctive chromatin modification patterns that combines the active histone H3K4me3 mark and the repressive H3K27me3 mark. These bivalent domains are considered to play a pivotal role related to pluripotency by maintaining lineage commitment programs in a poised state. Enhancers are long-range regulatory elements that enable precise tissue-specific gene expression patterns during development, which are marked by the presence of H3K4me1. However, how enhancers functional interact with bivalent promoters has remained elusive. Here, we identified thousands of enhancers and bivalent promoters through genome-wide epigenomic analysis in embryonic stem cells and neural progenitor cells. We found that bivalent promoters are significantly proximal to poised enhancers which are distinguished by the enrichment of H3K4me1 and the absence of the H3K27ac than active promoters. Upon differentiation from ES cells to NP cells, some de novo formed bivalent promoters enriched in nervous system development are found. We also find distinct classes of bivalent genes are differentially transcribed upon differentiation. Our findings will have implications in understanding the regulatory mechanisms that orchestrate the lineage differentiation process.