| Autor: |
Yu Jiang, Fei Huang, Lu Chen, Jia-Hui Gu, Yun-Wen Wu, Meng-Yan Jia, Zhen Lin, Yong Zhou, Yan-Chu Li, Chao Yu, Ming-Han Tong, Li Shen, Heng-Yu Fan, Qian-Qian Sha |
| Rok vydání: |
2022 |
| Předmět: |
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| Zdroj: |
Journal of advanced research. |
| ISSN: |
2090-1224 |
| Popis: |
The R-loop is a naturally formed three-strand nucleic acid structure that recently has been reported to participate in multiple biological processes and helped answer some previously unexplained scientific questions. Meiosis process involves multiple chromatin-related events such as DNA double-stranded breaks (DSB) formation, repairing and transcriptional dynamics.Explore the regulatory roles and physiological functions of R-loops in the mammalian meiosis process.In our study, using genome-wide S9.6 CUTTag seq, we first mapped the genomic distribution and dynamic changes of R-loop during the meiotic process in mice, from spermatogonia to secondary spermatocytes. And we further explore the role of R-loop in physiological conditions by constructing conditional knockout mice of Rnaseh1, which deleted the R-loop endonuclease before meiosis entry.R-loop predominantly distributes at promoter-related regions and varies across different meiotic stages. By joint analysis with the corresponding transcriptome, we found that the R-loop was closely related to transcription during the meiotic process. The high frequency of promoter-related R-loop in meiotic cells is usually accompanied by high transcription activity, and we further verified this in the leptotene/zygotene to the pachytene transition process. Moreover, the lack of RNase H1 caused sterility in male mice with R-loop accumulation and abnormal DSB repair in spermatocytes. Further analysis showed that abnormal R-loop accumulation in the leptotene/zygotene stages influenced transcriptional regulation in the pachytene stage.The mutual regulation of the R-loop and transcription plays an essential role in spermatogenesis. And R-loop is also important for the normal repair process of DSB during meiosis. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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