Dataset Information
Genome-wide map of R-loops reveals its interplay with transcription and genome integrity during germ cell meiosis.
Ontology highlight
ABSTRACT: Introduction
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.Objectives
Explore the regulatory roles and physiological functions of R-loops in the mammalian meiosis process.Methods
In our study, using genome-wide S9.6 CUT & Tag 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.Results
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.Conclusion
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.
SUBMITTER: Jiang Y
PROVIDER: S-EPMC10491972 | biostudies-literature | 2023 Sep
REPOSITORIES: biostudies-literature
Publications
Genome-wide map of R-loops reveals its interplay with transcription and genome integrity during germ cell meiosis.
Journal of advanced research 20221114
<h4>Introduction</h4>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.<h4>Objectives</h4>Explore the regulatory roles and physiological functions of R-loops in the mammalian meiosis ...[more]
