The lysine deacetylase activity of histone deacetylases 1 and 2 is required to safeguard zygotic genome activation in mice and cattle
The lysine deacetylase activity of histone deacetylases 1 and 2 is required to safeguard zygotic genome activation in mice and cattle
复制标题
组蛋白脱乙酰酶 1 和 2 的赖氨酸脱乙酰酶活性是保护小鼠和牛合子基因组激活所必需的
DOI：
10.1242/dev.200854
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发表时间：
2022-06-01
期刊：
影响因子：
4.6
通讯作者：
Zhang, Kun
中科院分区：
文献类型：
--
作者：
Dang, Yanna;Li, Shuang;Zhang, Kun
The genome is transcriptionally inert at fertilization and must be activated through a remarkable developmental process called zygotic genome activation (ZGA). Epigenetic reprogramming contributes significantly to the dynamic gene expression during ZGA; however, the mechanism has yet to be resolved. Here, we find histone deacetylases 1 and 2 (HDAC1/2) can regulate ZGA through lysine deacetylase activity. Notably, in mouse embryos, overexpression of a HDAC1/2 dominant-negative mutant leads to developmental arrest at the two-cell stage. RNA-seq reveals that 64% of downregulated genes are ZGA genes and 49% of upregulated genes are developmental genes. Inhibition of the deacetylase activity of HDAC1/2 causes a failure of histone deacetylation at multiple sites, including H4K5, H4K16, H3K14, H3K18 and H3K27. ChIP-seq analysis exhibits an increase and decrease of H3K27ac enrichment at promoters of up- and downregulated genes, respectively. Moreover, HDAC1 mutants prohibit the removal of H3K4me3 by impeding expression of Kdm5 genes. Importantly, the developmental block can be greatly rescued by Kdm5b injection and by partially correcting the expression of the majority of dysregulated genes. Similar functional significance of HDAC1/2 is conserved in bovine embryos. Overall, we propose that HDAC1/2 are indispensable for ZGA by creating correct transcriptional repressive and active states in mouse and bovine embryos.
