Genomewide decoupling of H2AK119ub1 and H3K27me3 in early mouse development  

小鼠早期胚胎发育中组蛋白修饰H2AK119ub1与H3K27me3的全基因组解偶联

作　　者：Yezhang Zhu Jiali Yu Yan Rong Yun-Wen Wu Yang Li Lejiao Zhang Yinghao Pan Heng-Yu Fan Li Shen 朱业张;俞佳丽;戎妍;吴韵雯;李阳;张乐姣;潘应昊;范衡宇;沈立(The MOE Key Laboratory of Biosystems Homeostasis&Protection and Zhejiang Provincial Key Laboratory for Cancer Molecular Cell Biology,Life Sciences Institute,Zhejiang University,Hangzhou 310058,China;Department of Orthopedics Surgery,the Second Affiliated Hospital,School of Medicine,Zhejiang University,Hangzhou 310009,China;Hangzhou Innovation Center,Zhejiang University,Hangzhou 311215,China)

机构地区：[1]The MOE Key Laboratory of Biosystems Homeostasis&Protection and Zhejiang Provincial Key Laboratory for Cancer Molecular Cell Biology,Life Sciences Institute,Zhejiang University,Hangzhou 310058,China [2]Department of Orthopedics Surgery,the Second Affiliated Hospital,School of Medicine,Zhejiang University,Hangzhou 310009,China [3]Hangzhou Innovation Center,Zhejiang University,Hangzhou 311215,China

出　　处：《Science Bulletin》2021年第24期2489-2497,M0004,共10页科学通报（英文版）

基　　金：supported by the National Natural Science Foundation of China(32022023 and 31871478);the National Key Research and Development Programs of China(2017YFC1001500);Zhejiang Provincial Natural Science Foundation of China(LR18C060001)。

摘　　要：Polycomb group(Pc G)proteins are crucial chromatin regulators during development.H2 AK119 ub1(H2 Aub)and H3 K27 me3 are catalyzed by Polycomb-repressive complex 1 and 2(PRC1/2)respectively,and they largely overlap in the genome due to mutual recruitment of the two complexes.However,it is unclear whether PRC1/H2 Aub and PRC2/H3 K27 me3 can also function independently.By developing an ultra-sensitive carrier-DNA-assisted chromatin immunoprecipitation sequencing method termed CATCH-Seq,we generated allelic H2 Aub profiles in mouse gametes and early embryos.Our results revealed an unexpected genomewide decoupling of H2 Aub and H3 K27 me3 in mouse preimplantation embryos,where H2 Aub but not H3 K27 me3 was enriched at Pc G targets while only H3 K27 me3 was deposited in the broad distal domains associated with DNA methylation-independent non-canonical imprinting.These observations suggest that H2 Aub represses future bivalent genes during early embryogenesis without H3 K27 me3,but it is not required for the maintenance of non-canonical imprinting,which is mediated by maternal H3 K27 me3.Thus,our study reveals the distinct depositions and independent functions of H2 Aub and H3 K27 me3 during early mammalian development.多梳家族蛋白(Polycomb group proteins)是发育过程中的关键染色质调控因子.组蛋白H2AK119位点的单泛素化修饰(H2AK119ub1,H2Aub)和组蛋白H3K27位点的三甲基化修饰(H3K27me3)分别是由多梳抑制复合体1(Polycomb Repressive Complex,PRC1)和2(PRC2)催化.由于PRC1和PRC2可以相互招募,H2Aub和H3K27me3这两种组蛋白修饰在基因组上表现出很大程度的重合与偶联.然而,它们是否能够独立存在并发挥功能仍然没有定论.本研究新开发了一种超灵敏微量染色质免疫共沉淀测序技术CATCH-Seq,并利用该技术发现H2Aub和H3K27me3在小鼠早期胚胎发育过程中呈现出全基因组范围的解偶联现象,即经典的多梳家族蛋白靶基因上仅有H2Aub的富集,而非经典基因印记区域仅有H3K27me3的富集.这些结果表明,H2Aub能够在早期胚胎发育阶段缺失H3K27me3的情况下负责沉默未来具有二价启动子的基因,但并不直接参与H3K27me3依赖的非经典印记基因的沉默.该工作揭示了H2Aub和H3K27me3这两种组蛋白修饰在哺乳动物早期胚胎发育中相互区别且独立的分布和功能.

关 键 词：POLYCOMB H2AK119ub1 H3K27me3 Preimplantation development Non-canonical imprinting 

分 类 号：Q344[生物学—遗传学]