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bioRxiv · 10.1101/2021.04.14.439777

Maternal and zygotic factors sequentially shape the tissue regionalization of chromatin landscapes in early vertebrate embryos

Paraiso, K. D.·Blitz, I. L.·Cho, K. W. Y.
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Abstract

One of the first steps in cellular differentiation of vertebrate embryos is the formation of the three germ layers. Maternal pioneer transcription factors (TFs) bind to the regulatory regions of the embryonic genome prior to zygotic genome activation and initiate germ layer specification. While the involvement of maternal TFs in establishing epigenetic marks in whole embryos was addressed previously, how early pluripotent cells acquire spatially restricted epigenetic identity in embryos remain unknown. Here, we report that the H3K4me1 enhancer mark in each germ layer becomes distinct in germ layer specific regulatory regions, forming super-enhancers (SEs), by early gastrula stage. Distinct SEs are established in these germ layers near robustly regulated germ layer identity genes, suggesting that SEs are important for the canalization of development. Establishment of these enhancers requires a sequential function of maternal and zygotic TFs. By knocking down the expression of a critical set of maternal endodermal TFs, an overwhelming majority of the endodermal H3K4me1 marks are lost. Interestingly, this disappearance of endodermal marking coincides with the appearance of ectodermal and mesodermal H3K4me1 marks in the endoderm, suggesting a transformation in the chromatin state of these nuclei towards a more ecto-mesodermal state. De novo motif analysis to identify TFs responsible for the transformation recovers a profile for endodermal maternal TFs as well as their downstream target TFs. We demonstrate the importance of coordinated activities of maternal and zygotic TFs in defining a spatially resolved dynamic process of chromatin state establishment.

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Paraiso, K. D., Blitz, I. L., Cho, K. W. Y.. 2021-04-14. Maternal and zygotic factors sequentially shape the tissue regionalization of chromatin landscapes in early vertebrate embryos. https://doi.org/10.1101/2021.04.14.439777

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