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bioRxiv · 10.1101/2021.03.16.435592

Establishment of Developmental Gene Silencing by Ordered Polycomb Complex Recruitment in Early Zebrafish Embryos

Cairns, B. R.·Hickey, G. J. M.·Wike, C.·Nie, X.·Guo, Y.·Murphy, P. J.·Tan, M.
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Abstract

Vertebrate embryos achieve developmental competency during zygotic genome activation (ZGA) by establishing chromatin states that silence yet poise developmental genes for subsequent lineage-specific activation. Here, we reveal how developmental gene poising is established de novo in preZGA zebrafish embryos. Poising is established at promoters and enhancers that initially contain open/permissive chromatin with Placeholder nucleosomes (bearing H2A.Z, H3K4me1, and H3K27ac), and DNA hypomethylation. Silencing is initiated by the recruitment of Polycomb Repressive Complex 1 (PRC1), and H2Aub1 deposition by catalytic Rnf2 during preZGA and ZGA stages. During postZGA, H2Aub1 enables Aebp2-containing PRC2 recruitment and H3K27me3 deposition. Notably, preventing H2Aub1 (via Rnf2 inhibition) eliminates recruitment of Aebp2-PRC2 and H3K27me3, and elicits transcriptional upregulation of certain developmental genes during ZGA. However, upregulation is independent of H3K27me3 - establishing H2Aub1 as the critical silencing modification at ZGA. Taken together, we reveal the logic and mechanism for establishing poised/silent developmental genes in early vertebrate embryos. Impact StatementDe novo polycomb domains are formed in zebrafish early embryos by focal histone H2Aub1 deposition by Rnf2-PRC1 - which imposes transcription silencing - followed by subsequent recruitment of Aebp2-PRC2 and H3K27me3 deposition.

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Cairns, B. R., Hickey, G. J. M., Wike, C., Nie, X., Guo, Y., Murphy, P. J., Tan, M.. 2021-03-16. Establishment of Developmental Gene Silencing by Ordered Polycomb Complex Recruitment in Early Zebrafish Embryos. https://doi.org/10.1101/2021.03.16.435592

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