AI Article Synopsis
- Around implantation, the epiblast transitions from naïve to primed pluripotency, crucial for developing three germ layers.
- A genome-wide study reveals that enhancers in the ectoderm are already accessible in early embryonic development, alongside a formation of bivalency in developmental gene promoters due to specific histone modifications.
- The study highlights the importance of the enzyme KMT2B in establishing this unique chromatin state, which is vital for activating developmental genes and preventing embryonic lethality.
Article Abstract
Around implantation, the epiblast (Epi) transits from naïve to primed pluripotency, before giving rise to the three germ layers. How chromatin is reconfigured during this developmental window remains poorly understood. We performed a genome-wide investigation of chromatin landscapes during this period. We find that enhancers in ectoderm are already pre-accessible in embryonic day 6.5 (E6.5) Epi when cells enter a primed pluripotent state. Unexpectedly, strong trimethylation of histone H3 at lysine 4 (H3K4me3) emerges at developmental gene promoters in E6.5 Epi and positively correlates with H3K27me3, thus establishing bivalency. These genes also show enhanced spatial interactions. Both the strong bivalency and spatial clustering are virtually absent in preimplantation embryos and are markedly reduced in fate-committed lineages. Finally, we show that KMT2B is essential for establishing bivalent H3K4me3 at E6.5 but becomes partially dispensable later. Its deficiency leads to impaired activation of developmental genes and subsequent embryonic lethality. Thus, our data characterize lineage-specific chromatin reconfiguration and a unique chromatin state for primed pluripotency.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7362285 | PMC |
| http://dx.doi.org/10.1038/s41588-019-0545-1 | DOI Listing |
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