Dynamic Change of R-Loop Implicates in the Regulation of Zygotic Genome Activation in Mouse

作者：Hyeonji Lee, Seong-Yeob You, Dong‐Wook Han, Hyeonwoo La, Chanhyeok Park, Seonho Yoo, Kiye Kang, Min-Hee Kang, Youngsok Choi, Kwonho Hong · 发表于：International Journal of Molecular Sciences · 年份：2022 · DOI：10.3390/ijms232214345 · 被引用次数：6 · 研究领域：DNA Repair Mechanisms、Genomics and Chromatin Dynamics、CRISPR and Genetic Engineering

In mice, zygotic genome activation (ZGA) occurs in two steps: minor ZGA at the one-cell stage and major ZGA at the two-cell stage. Regarding the regulation of gene transcription, minor ZGA is known to have unique features, including a transcriptionally permissive state of chromatin and insufficient splicing processes. The molecular characteristics may originate from extremely open chromatin states in the one-cell stage zygotes, yet the precise underlying mechanism has not been well studied. Recently, the R-loop, a triple-stranded nucleic acid structure of the DNA/RNA hybrid, has been implicated in gene transcription and DNA replication. Therefore, in the present study, we examined the changes in R-loop dynamics during mouse zygotic development, and its roles in zygotic transcription or DNA replication. Our analysis revealed that R-loops persist in the genome of metaphase II oocytes and preimplantation embryos from the zygote to the blastocyst stage. In particular, zygotic R-loop levels dynamically change as development proceeds, showing that R-loop levels decrease as pronucleus maturation occurs. Mechanistically, R-loop dynamics are likely linked to ZGA, as inhibition of either DNA replication or transcription at the time of minor ZGA decreases R-loop levels in the pronuclei of zygotes. However, the induction of DNA damage by treatment with anticancer agents, including cisplatin or doxorubicin, does not elicit genome-wide changes in zygotic R-loop levels. Therefore, our study...