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Genome-wide Map of R-loops Reveals its interplays with Transcription and Genome Integrity during Germ Cell Meiosis

ABSTRACT: Genome-wide Map of R-loops Reveals its interplays with Transcription and Genome Integrity during Germ Cell Meiosis

PROVIDER: PRJNA796035 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR17535900_1.fastq.gz	Fastqsanger.gz
	SRR17535900_2.fastq.gz	Fastqsanger.gz
	SRR17535901_1.fastq.gz	Fastqsanger.gz
	SRR17535901_2.fastq.gz	Fastqsanger.gz
	SRR17535902_1.fastq.gz	Fastqsanger.gz

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Genome-wide Map of R-loop Reveals its interplays with Transcription and Genome Integrity during Germ Cell Meiosis

Project description:Genome-wide Map of R-loop Reveals its interplays with Transcription and Genome Integrity during Germ Cell Meiosis

| PRJNA787109 | ENA

Genome-wide Map of R-loops Reveals its interplays with Transcription and Genome Integrity during Germ Cell Meiosis

Project description:R-loop is a naturally formed three-strand nucleic acid structure that was reported to take part in multiple biological processes. In our study, we firstly mapped R-loop genomic distribution in mammalian meiotic cells by genome-wide S9.6 CUT & Tag seq. R-loop mainly distributed at promoter-related regions, and combined with systematically transcriptome analysis showed R-loop was closely related to transcription in the meiotic process. Moreover, we verified the conclusion by constructing conditional knockout mice of Rnaseh1, which delete the R-loop endonuclease before meiosis entry. Lack of RNase H1 caused mice completely sterile with R-loop accumulation and abnormal DSB repairing in spermatocytes. Further analysis showed R-loop accumulation in leptotene/zygotene influenced transcriptional regulation in the pachytene stage. Thus, mutual regulation of R-loop and transcription plays an essential role in spermatogenesis.

2023-02-01 | GSE193401 | GEO

Genome-wide map of R-loops reveals its interplay with transcription and genome integrity during germ cell meiosis.

Project description:IntroductionThe 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.ObjectivesExplore the regulatory roles and physiological functions of R-loops in the mammalian meiosis process.MethodsIn 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.ResultsR-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.ConclusionThe 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.

| S-EPMC10491972 | biostudies-literature

Genome-wide Map of R-loop Reveals its interplays with Transcription and Genome Integrity during Germ Cell Meiosis

Project description:R-loop is a three-strand nucleic acid structure composed of mRNA and DNA. In mammalian meiotic cells, R-loop mainly distributed at promoter-related regions, and combined with systematically transcriptome analysis showed R-loop was closely related to transcription in meiotic process. Moreover, knockout of Rnaseh1 in meiotic cells caused mice completely sterile with R-loop accumulation and abnormal DSB repairing in spermatocytes. Further analysis showed R-loop accumulation in leptotene/zygotene influenced transcriptional regulation in pachytene stage. Thus, mutual regulation of R-loop and transcription plays essential role in spermatogenesis.

2023-09-21 | GSE190430 | GEO

PSIP1/LEDGF reduces R-loops at transcription sites and maintain genome integrity

Project description:PSIP1/LEDGF reduces R-loops at transcription sites and maintain genome integrity

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DNA polymerase ε harmonizes topological states and R-loops formation to maintain genome integrity in Arabidopsis

Project description:Genome topology is tied to R-loop formation and genome stability. However, the regulatory mechanism remains to be elucidated. By establishing a system to sense the connections between R-loops and genome topology states, we show that inhibiting DNA topoisomerase 1 (TOP1i) triggers the global increase of R-loops (called topoR-loops) and DNA damages, which are exacerbated in the DNA damage repair-compromised mutant atm. Further suppressor screen identifies a mutation in POL2A, the catalytic subunit of DNA polymerase ?, liberating the TOP1i-induced topoR-loop accumulation and genome instability in atm. Additionally, we find a highly conserved junction domain between the exonuclease and polymerase domains in POL2A that is required for modulating topoR-loops near DNA replication origins and facilitating faithful DNA replication. Our results suggest that DNA replication is in concert with genome topological states to fine-tune R-loops and thereby maintain genome integrity, revealing a presumably conserved regulatory mechanism of TOP1i resistance in chemotherapy for ATM-deficient cancers.

2023-11-03 | GSE216170 | GEO

PSIP1/LEDGF reduces R-loops at transcription sites and maintain genome integrity (TT-Seq)

Project description:R-loops are transcriptional by-products that pose a persistent threat to genome integrity and are implicated in accelerated ageing and cancer. PSIP1/LEDGF is a multifunctional chromatin protein that associates with transcriptional elongation machinery. Here, we demonstrated that PSIP1 interacts with R-loops generated at the site of transcription and along with the factors involved in R-loop resolution, including PARP1. Reduced PSIP1 levels in human and mouse cells lead to an increase in R-loop levels and DNA damage at the PSIP1 binding sites. This increased R-loops and DNA damage was specific at the RNA polymerase II transcription sites, causing local transcriptional arrest. In addition, we demonstrate that PSIP1 can be targeted for increasing the sensitivity of cancer cells to PARP1 inhibitors and transcription-coupled DNA damaging agents. These findings show the critical role of PSIP1 in reducing the R-loop burden and DNA damage at the transcriptionally active regions of the genome.

2023-12-08 | GSE220233 | GEO

PSIP1/LEDGF reduces R-loops at transcription sites and maintain genome integrity (RNA-Seq)

2023-12-08 | GSE220232 | GEO

PSIP1/LEDGF reduces R-loops at transcription sites and maintain genome integrity (CUT&Tag-Seq)

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PSIP1/LEDGF reduces R-loops at transcription sites and maintain genome integrity (HEK293T CUT&Tag-Seq)

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