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bioRxiv · 10.1101/557082

Quantitative multiplexed ChIP reveals global alterations that shape promoter bivalency in ground state embryonic stem cells

Kumar, B.·Elsässer, S. J.
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Abstract

To understand the epigenetic foundation of naive pluripotent cells, we implement a quantitative multiplexed ChIP-Seq method (MINUTE-ChIP) comparing mouse ESC grown in 2i versus Serum conditions. Combined with quantitative western blot and mass spectrometry, we find compelling evidence for a broad H3K27me3 hypermethylation of the genome, concomitant with the widespread loss of DNA CpG methylation. We show that opposing action of EZH2 and JMJD3/UTX shape the H3K27me3 landscape, with almost all bivalent promoters stably retaining high H3K27me3 levels in 2i. In parallel, we show a mechanistically uncoupled, global decrease of H3K4me3 and strong reduction at bivalent promoters, suggesting that low H3K4me3 and high H3K27me3 levels at bivalent promoters safeguard naive pluripotency.

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Kumar, B., Elsässer, S. J.. 2019-03-06. Quantitative multiplexed ChIP reveals global alterations that shape promoter bivalency in ground state embryonic stem cells. https://doi.org/10.1101/557082

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