CHAF1b, chromatin assembly factor-1 subunit b, is essential for mouse preimplantation embryos
CHAF1b, chromatin assembly factor-1 subunit b, is essential for mouse preimplantation embryos
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CHAF1b（染色质组装因子 1 亚基 b）对于小鼠植入前胚胎至关重要
DOI：
10.1016/j.ijbiomac.2021.11.181
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发表时间：
2022
影响因子：
8.2
通讯作者：
Su Jianmin
中科院分区：
文献类型：
--
作者：
Zhang Yingbing;Yang Ying;Qiao Peipei;Wang Xiyue;Yu Ruiluan;Sun Hongzheng;Xing Xupeng;Zhang Yong;Su Jianmin
染色质组装因子-1（Chromatin assembly factor-1，subunit B，CHAF 1 B）是染色质组装因子-1（chromatin assembly factor-1，CAF-1）复合物的p60亚基，是一种进化上保守的蛋白质，参与多种生物学过程。尽管CHAF 1b具有多种功能，但其在植入前胚胎中的功能仍然不清楚。在本研究中，我们发现CHAF 1b基因敲低不影响囊胚率，但导致囊胚孵化率低，体外生长失败，体内胚胎死亡。值得注意的是，CHAF 1b耗竭增加了细胞凋亡，并导致细胞命运规范的关键调节因子（包括Oct 4，Cdx 2，Sox 2和Nanog）的表达下调。进一步的分析表明，CHAF 1b介导H3.3被H3.1/3.2取代，这与抑制性组蛋白标记（H3 K9 me 2/3和H3 K27 me 2/3）减少和活性组蛋白标记（H3 K4 me 2/3）增加有关。此外，RNA测序分析显示，CHAF 1b缺失导致1508个基因的差异表达，包括表观遗传修饰基因，多个谱系特异性基因和几个编码凋亡蛋白的基因。此外，转座酶可及染色质测序分析表明，沉默CHAF 1b改变了谱系特异性基因和表观遗传修饰基因的染色质可及性。综上所述，这些数据表明CHAF 1b在植入前胚胎中起着重要作用，可能是通过调节表观遗传修饰和谱系特化。
Chromatin assembly factor-1, subunit b (CHAF1b), the p60 subunit of the chromatin-assembly factor-1 (CAF-1) complex, is an evolutionarily conserved protein that has been implicated in various biological processes. Although a variety of functions have been attributed to CHAF1b, its function in preimplantation embryos remains obscure. In this study, we showed that CHAF1b knockdown did not affect the blastocyst rate, but resulted in a low blastocyst hatching rate, outgrowth failurein vitro, and embryonic lethality after implantationin vivo. Notably, CHAF1b depletion increased apoptosis and caused down-regulated expression of key regulators of cell fate specification, including Oct4, Cdx2, Sox2, and Nanog. Further analysis revealed that CHAF1b mediated the replacement of H3.3 with H3.1/3.2, which was associated with decreased repressive histone marks (H3K9me2/3 and H3K27me2/3) and increased active histone marks (H3K4me2/3). Moreover, RNA-sequencing analysis revealed that CHAF1b depletion resulted in the differential expression of 1508 genes, including epigenetic modifications genes, multiple lineage-specific genes, and several genes encoding apoptosis proteins. In addition, assay for transposase-accessible chromatin-sequencing analysis demonstrated that silencing CHAF1b altered the chromatin accessibility of lineage-specific genes and epigenetic modifications genes. Taken together, these data imply that CHAF1b plays significant roles in preimplantation embryos, probably by regulating epigenetic modifications and lineage specification.