Abstract
Monomethylation on lysine 4 of histone H3 (H3K4me1) is commonly associated with distal enhancers, but H3K4me1 is also present at promoter regions proximal to transcription start sites. To assess a possible role for H3K4me1 in dictating gene regulatory states at promoters, we examined H3K4me1 peak density around promoters in human and mouse germ cells using an analytic strategy that allowed us to assess relationships between different epigenetic marks on a promoter-by-promoter basis. We found that H3K4me1 exhibits either a bimodal pattern at active promoters, where it flanks H3K4me3, or a unimodal pattern at poised promoters, where it coincides with both H3K4me3 and H3K27me3. This pattern is correlated with gene expression level, but is more strongly linked to a poised chromatin state, defined by the simultaneous presence of H3K4me3 and H3K27me3, than to transcriptional activity. The pattern is especially prominent in germ cells, but is also present in other cell types, including embryonic stem cells and differentiated somatic cells. We propose that H3K4me1 is a key feature of the poised epigenetic state, and suggest possible roles for this mark in epigenetic memory.
Highlights
Post-translational modifications on histone tails are closely correlated to transcriptional states
We set out to examine H3K4me1 distribution in germ cells and embryonic stem cells (ESCs), cell types that share many regulatory mechanisms related to reprogramming and pluripotency
1https://github.com/Lesch-Lab/H3K4me1-profiles unit distance from each peak to the nearest transcription start sites (TSS) and visualized the distribution of peak distances with a density plot, where the y axis shows the probability that the nearest peak is centered a given distance away from the TSS (Figure 1A)
Summary
Post-translational modifications on histone tails are closely correlated to transcriptional states. An alternative view suggests that promoters and enhancers are a single class of transcriptional elements distinguished by different levels of transcription, and the varying H3K4me to H3K4me signal ratio at promoters compared to enhancers reflects the rates at which the elements recruit RNA Polymerase II (Core et al, 2014; Andersson et al, 2015) Cell type is another aspect of regulatory context that may play a role in H3K4me function. We report distinct patterns of H3K4me that predict transcriptional regulatory states at promoters in germ cells and ESCs. We used an alternative approach to ChIP-seq data analysis in which we summarized chromatin signal around promoters based on ChIP-seq peak density instead of signal density. We conclude that unimodal H3K4me centered on the TSS is a characteristic feature of the poised epigenetic state in ESCs and germ cells
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