Establishment of developmental gene silencing by ordered polycomb complex recruitment in early zebrafish embryos

eLife

Bradley R Cairns¹  Xichen Nie¹  Candice L Wike¹  Graham JM Hickey¹  Yixuan Guo¹  Mengyao Tan¹  Patrick J Murphy² 

[1] Howard Hughes Medical Institute, Department of Oncological Sciences and Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, United States;Howard Hughes Medical Institute, Department of Oncological Sciences and Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, United States;Department of Biomedical Genetics, Wilmot Cancer Center, University of Rochester School of Medicine, Rochester, United States;

关键词: chromatin;    polycomb;    ubiquitylation;    Placeholder;    zygotic genome activation;    development;    Zebrafish;   

DOI  :  10.7554/eLife.67738

来源: eLife Sciences Publications, Ltd

【 摘 要 】

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.

【 授权许可】

CC BY