Abstract
In embryonic stem (ES) cells, developmental regulators have a characteristic bivalent chromatin signature marked by simultaneous presence of both activation (H3K4me3) and repression (H3K27me3) signals and are thought to be in a ‘poised’ state for subsequent activation or silencing during differentiation. We collected eleven pairs (H3K4me3 and H3K27me3) of ChIP sequencing datasets in human ES cells and eight pairs in murine ES cells, and predicted high-confidence (HC) bivalent promoters. Over 85% of H3K27me3 marked promoters were bivalent in human and mouse ES cells. We found that (i) HC bivalent promoters were enriched for developmental factors and were highly likely to be differentially expressed upon transcription factor perturbation; (ii) murine HC bivalent promoters were occupied by both polycomb repressive component classes (PRC1 and PRC2) and grouped into four distinct clusters with different biological functions; (iii) HC bivalent and active promoters were CpG rich while H3K27me3-only promoters lacked CpG islands. Binding enrichment of distinct sets of regulators distinguished bivalent from active promoters. Moreover, a ‘TCCCC’ sequence motif was specifically enriched in bivalent promoters. Finally, this analysis will serve as a resource for future studies to further understand transcriptional regulation during embryonic development.
Highlights
In embryonic stem (ES) cells, developmental regulators have a characteristic bivalent chromatin signature marked by simultaneous presence of both activation (H3K4me3) and repression (H3K27me3) signals and are thought to be in a ‘poised’ state for subsequent activation or silencing during differentiation
High-confidence bivalent promoters in human and mouse ES cells are enriched for developmental regulators
There are other factors contributing to the variation between samples, for example ES cells were grown in diverse culture conditions, and using different cell lines as well as various antibodies across datasets (Tables S1 and S2)
Summary
In embryonic stem (ES) cells, developmental regulators have a characteristic bivalent chromatin signature marked by simultaneous presence of both activation (H3K4me3) and repression (H3K27me3) signals and are thought to be in a ‘poised’ state for subsequent activation or silencing during differentiation. Set/MLL histone methyltransferases, the mammalian homologues of the trithorax group proteins (trxG), catalyse the H3K4me[3] marks and Polycomb (PcG) group proteins catalyse H3K27me[3] We performed a systematic identification and characterisation of bivalent genes and their functions by integrating all publicly available pairs (H3K4me[3] and H3K27me[3] measured on the same samples) of ChIP sequencing datasets in human and mouse ES cells, and identified and characterised a set of 4,979 and 3,659 high–confidence (HC) bivalent promoters respectively
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