Establishment of developmental gene silencing by ordered polycomb complex recruitment in early zebrafish embryos.
Establishment of developmental gene silencing by ordered polycomb complex recruitment in early zebrafish embryos.
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DOI：
10.7554/elife.67738
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发表时间：
2022-01-04
期刊：
影响因子：
7.7
通讯作者：
Cairns BR
中科院分区：
文献类型：
--
作者：
Hickey GJ;Wike CL;Nie X;Guo Y;Tan M;Murphy PJ;Cairns BR
脊椎动物胚胎在合子基因组激活（ZGA）过程中通过建立染色质状态来实现发育能力，该状态沉默但平衡发育基因以进行随后的谱系特异性激活。在这里，我们揭示了在 preZGA 斑马鱼胚胎中建立发育基因平衡时染色质状态的顺序。平衡是在启动子和增强子上建立的，这些启动子和增强子最初包含带有“占位符”核小体（带有 H2A.Z、H3K4me1 和 H3K27ac）的开放/允许染色质和 DNA 低甲基化。在 preZGA 和 ZGA 阶段，多梳抑制复合物 1 (PRC1) 的招募和催化 Rnf2 沉积 H2Aub1 会引发沉默。在ZGA后期间，H2Aub1使得含有Aebp2的PRC2招募和H3K27me3沉积成为可能。值得注意的是，阻止 H2Aub1（通过抑制 Rnf2）会消除 Aebp2-PRC2 和 H3K27me3 的募集，并在 ZGA 期间引发某些发育基因的转录上调。然而，上调与 H3K27me3 无关——将 H2Aub1 确立为 ZGA 的关键沉默修饰。总之，我们揭示了在早期脊椎动物胚胎中建立平衡/沉默发育基因的逻辑和机制。
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.