Intragenic DNA methylation regulates insect gene expression and reproduction through the MBD/Tip60 complex.
Intragenic DNA methylation regulates insect gene expression and reproduction through the MBD/Tip60 complex.
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基因内 DNA 甲基化通过 MBD/Tip60 复合体调节昆虫基因表达和繁殖
DOI：
10.1016/j.isci.2021.102040
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发表时间：
2021-02-19
期刊：
影响因子：
5.8
通讯作者：
Zheng S
中科院分区：
文献类型：
--
作者：
Xu G;Lyu H;Yi Y;Peng Y;Feng Q;Song Q;Gong C;Peng X;Palli SR;Zheng S
DNA甲基化是一种重要的表观遗传修饰。然而，昆虫基因内DNA甲基化的调控和功能尚不清楚。在这里，我们表明，涉及基因内DNA甲基化的调控机制控制卵巢和胚胎发育过程中的家蚕。在B. mori中，在卵巢基因的转录起始位点（TSS）附近发现DNA甲基化。通过启动子活性分析，我们观察到5′ UTR甲基化增强基因表达。此外，甲基DNA结合域蛋白2/3（MBD 2/3）结合基因内甲基CpG片段并募集乙酰转移酶Tip 60以促进组蛋白H3 K27乙酰化和基因表达。此外，全基因组分析表明，H3 K27乙酰化的峰值出现在甲基修饰基因的TSS附近，并且DNA甲基化在参与B. mori卵巢中蛋白质合成的基因中富集，MBD 2/3敲低导致繁殖力降低。这些数据揭示了基因体甲基化调控昆虫基因表达和繁殖的机制。昆虫基因内5 mC通过组蛋白H3 K27乙酰化增强基因表达MBD 2/3结合基因内5 mC并募集Tip 60促进H3 K27乙酰化基因内5 mC修饰昆虫卵巢中蛋白质合成相关基因内5 mC在昆虫生殖中起作用昆虫学;基因调控的分子机制;组学
DNA methylation is an important epigenetic modification. However, the regulations and functions of insect intragenic DNA methylation remain unknown. Here, we demonstrate that a regulatory mechanism involving intragenic DNA methylation controls ovarian and embryonic developmental processes in Bombyx mori. In B. mori, DNA methylation is found near the transcription start site (TSS) of ovarian genes. By promoter activity analysis, we observed that 5′ UTR methylation enhances gene expression. Moreover, methyl-DNA-binding domain protein 2/3 (MBD2/3) binds to the intragenic methyl-CpG fragment and recruits acetyltransferase Tip60 to promote histone H3K27 acetylation and gene expression. Additionally, genome-wide analyses showed that the peak of H3K27 acetylation appears near the TSS of methyl-modified genes, and DNA methylation is enriched in genes involved in protein synthesis in the B. mori ovary, with MBD2/3 knockdown resulting in decreased fecundity. These data uncover a mechanism of gene body methylation for regulating insect gene expression and reproduction. Insect intragenic 5mC enhances gene expression through histone H3K27 acetylation MBD2/3 binds the intragenic 5mC and recruits Tip60 to promote H3K27 acetylation Intragenic 5mCs modify protein synthesis-related genes in insect ovaries The intragenic 5mC plays a role in insect reproduction Entomology; molecular mechanism of gene regulation; omics
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