TY - JOUR TI - Establishment of developmental gene silencing by ordered polycomb complex recruitment in early zebrafish embryos AU - Hickey, Graham JM AU - Wike, Candice L AU - Nie, Xichen AU - Guo, Yixuan AU - Tan, Mengyao AU - Murphy, Patrick J AU - Cairns, Bradley R A2 - Chen, Xin A2 - White, Richard M A2 - Kaufman, Charles K VL - 11 PY - 2022 DA - 2022/01/04 SP - e67738 C1 - eLife 2022;11:e67738 DO - 10.7554/eLife.67738 UR - https://doi.org/10.7554/eLife.67738 AB - 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 the order of chromatin states in establishing developmental gene poising 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. KW - chromatin KW - polycomb KW - ubiquitylation KW - Placeholder KW - zygotic genome activation KW - development JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -