Linker histone H1FOO is required for bovine preimplantation development by regulating lineage specification and chromatin structure†
Linker histone H1FOO is required for bovine preimplantation development by regulating lineage specification and chromatin structure†
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连接组蛋白 H1FOO 是牛植入前发育所必需的，可调节谱系规格和染色质结构
DOI：
10.1093/biolre/ioac167
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发表时间：
2022-08-24
影响因子：
3.6
通讯作者：
Zhang, Kun
中科院分区：
文献类型：
--
作者：
Li, Shuang;Shi, Yan;Zhang, Kun
接头组蛋白H1与核小体结合，并参与染色质结构和功能的调节。H1变体H1 FOO在卵母细胞和早期胚胎中大量表达。然而，由于哺乳动物中H1 FOO的同源性较差，H1 FOO在植入前胚胎发育过程中的功能作用在很大程度上仍然未知，特别是在家畜中。在这里，我们发现H1 FOO不仅在卵母细胞和植入前胚胎中表达，而且在牛的颗粒细胞和精子细胞中表达。然后，我们证明了H1 FOO的干扰导致牛的植入前胚胎发育停滞，使用RNA编辑或Trim-Away方法。H1 FOO缺失导致桑椹胚阶段关键谱系特异性基因的表达受损，并影响细胞极性的建立。有趣的是，H1 FOO缺失导致编码其他接头H1和核心组蛋白的基因的表达显著增加。同时，存在抑制性染色质的两个标记H3 K9 me 3和H3 K27 me 3的增加和开放染色质的标记H4 K16 ac的减少。重要的是，牛H1 FOO的过度表达导致严重的胚胎发育缺陷。总之，我们建议，H1 FOO控制适当的染色质结构，这是至关重要的保真度的细胞极化和谱系规范在牛植入前的发展。
Linker histone H1 binds to the nucleosome and is implicated in the regulation of the chromatin structure and function. The H1 variant H1FOO is heavily expressed in oocytes and early embryos. However, given the poor homology of H1FOO among mammals, the functional role of H1FOO during preimplantation embryonic development remains largely unknown, especially in domestic animals. Here, we find that H1FOO is not only expressed in oocytes and preimplantation embryos but granulosa cells and spermatids in cattle. We then demonstrate that the interference of H1FOO results in preimplantation embryonic developmental arrest in cattle using either RNA editing or Trim-Away approach. H1FOO depletion leads to a compromised expression of critical lineage-specific genes at the morula stage and affects the establishment of cell polarity. Interestingly, H1FOO depletion causes a significant increase in the expression of genes encoding other linker H1 and core histones. Concurrently, there is an increase of H3K9me3 and H3K27me3, two markers of repressive chromatin and a decrease of H4K16ac, a marker of open chromatin. Importantly, overexpression of bovine H1FOO results in severe embryonic developmental defects. In sum, we propose that H1FOO controls the proper chromatin structure that is crucial for the fidelity of cell polarization and lineage specification during bovine preimplantation development.