iScience
Volume 24, Issue 2, 19 February 2021, 102040
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Article
Intragenic DNA methylation regulates insect gene expression and reproduction through the MBD/Tip60 complex

https://doi.org/10.1016/j.isci.2021.102040Get rights and content
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Highlights

  • 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

Summary

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.

Subject areas

Entomology
molecular mechanism of gene regulation
omics

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