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C19ORF84 connects piRNA and DNA methylation machineries to defend the mammalian germ line

ABSTRACT: C19ORF84 connects piRNA and DNA methylation machineries to defend the mammalian germ line

PROVIDER: PRJNA818177 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR18396425.fastq.gz	Fastqsanger.gz
	SRR18396426.fastq.gz	Fastqsanger.gz
	SRR18396427.fastq.gz	Fastqsanger.gz
	SRR18396428.fastq.gz	Fastqsanger.gz
	SRR18396429.fastq.gz	Fastqsanger.gz

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Similar Datasets

C19ORF84 connects piRNA and DNA methylation machineries to defend the mammalian germline

Project description:C19ORF84 connects piRNA and DNA methylation machineries to defend the mammalian germline

| PRJEB51968 | ENA

C19ORF84 connects piRNA and DNA methylation machineries to defend the mammalian germ line

Project description:In the male mouse germline, PIWI-interacting RNAs (piRNAs) bound to the PIWI protein MIWI2 guide the DNA methylation of young active transposable elements (TEs) through SPOCD1. We identified loss-of-function variants in the human SPOCD1 gene that cause male infertility and defective TE silencing. One of the SPOCD1 pathogenic alleles encodes a truncated protein that lacks the conserved carboxy-terminus. We discovered that this deleted region interacts with C19ORF84. In mouse foetal germ cells, C19ORF84 is a nuclear protein that is required for the association of SPOCD1 with DNMT3L, an essential component of the de novo methylation machinery. In summary, we found a conserved role for SPOCD1 in safeguarding the continuity of the human germline and discovered C19ORF84, an uncharacterised protein essential for orchestrating piRNA-directed DNA methylation.

2024-02-11 | GSE199038 | GEO

C19ORF84 connects piRNA and DNA methylation machineries to defend the mammalian germ line.

Project description: Not available

| S-EPMC10960678 | biostudies-literature

C19ORF84 connects piRNA and DNA methylation machineries to defend the mammalian germline

Project description:In the male mouse germline, PIWI-interacting RNAs (piRNAs), bound by the PIWI protein MIWI2 (PIWIL4), guide the DNA methylation of young active transposable elements (TEs) through SPOCD1. We identified loss-of-function variants in human SPOCD1 that cause male infertility and defective TE silencing. One SPOCD1 pathogenic allele encodes a truncated protein that lacks the conserved carboxy-terminus. We demonstrated that this deleted region interacts with C19ORF84. In mouse foetal germ cells, the nuclear protein C19ORF84 is required for the association of SPOCD1 with DNMT3L, an essential component of the de novo methylation machinery. In summary, we identified a conserved role for SPOCD1 in safeguarding the continuity of the human germline and discovered C19ORF84, an uncharacterised protein essential for 15 orchestrating piRNA-directed DNA methylation.

2024-02-13 | E-MTAB-11612 | biostudies-arrayexpress

C19ORF84 connects piRNA and DNA methylation machineries to defend the mammalian germline

Project description:In the male mouse germline, PIWI-interacting RNAs (piRNAs), bound by the PIWI protein MIWI2 (PIWIL4), guide DNA methylation of young active transposons through SPOCD1. However, the underlying mechanisms of SPOCD1-mediated piRNA-directed transposon methylation and whether this pathway functions to protect the human germline remains unknown. We identified loss-of-function variants in human SPOCD1 that cause defective transposon silencing and male infertility. Through the analysis of one of these pathogenic alleles, we discovered that the uncharacterised protein C19ORF84 interacts with SPOCD1. DNMT3C, the DNA methyltransferase responsible for transposon methylation, associates with SPOCD1 and C19ORF84 in foetal gonocytes. Furthermore, C19ORF84 is essential for piRNA-directed DNA methylation and male mouse fertility. Finally, C19ORF84 mediates the in vivo association of SPOCD1 with the de novo methylation machinery. In summary, we have discovered a conserved role for the human piRNA pathway in transposon silencing and C19ORF84, an uncharacterised protein essential for orchestrating piRNA-directed DNA methylation.

2024-02-14 | PXD047331 | Pride

Nucleoporin complex NPP-14/24 shape perinuclear germ granule architecture and coordinate piRNA silencing

Project description:Germ granules are RNA-rich biomolecular condensates regulating posttranscriptional gene expression. In C. elegans, germ granules are associated with the NPC. Mechanism by which germ granules associate with the nucleus and relevant functions remain unknown. We uncovered the function of the NPP-14/24 complex in spatially organizing perinuclear germ granules and fine-tuning the piRNA-based transcriptome surveillance and the inheritance of gene silencing.

2025-04-14 | PXD051572 | Pride

GLH/VASA helicases promote germ granule formation to ensure the fidelity of piRNA-mediated transcriptome surveillance

Project description:The ability to distinguish non-self from self is the key characteristic for any defense system. piRNAs function as guardians of the genome by silencing non-self nucleic acids and transposable elements in animals. Many piRNA factors are enriched in perinuclear germ granules, but whether their localization is required for piRNA biogenesis or function is not known. Here we show that GLH/VASA helicase mutants exhibit defects in forming perinuclear condensates containing PIWI and other small RNA cofactors. These mutant animals produce largely normal levels of piRNA but are defective in triggering piRNA silencing. Strikingly, while many piRNA targets are activated in GLH mutants, we observed that hundreds of endogenous genes are aberrantly silenced by piRNAs. This defect in self versus non-self recognition was also observed in other mutants where perinuclear P granules are disrupted. Together, our results argue that perinuclear germ granules function critically to promote the fidelity of piRNA-based transcriptome surveillance in C. elegans and preserve self versus non-self distinction.

2022-08-05 | PXD033506 | Pride

Modulation of Aub–Tdrd interactions elucidates piRNA amplification and germ plasm formation

Project description:Aub protein guided by piRNAs ensures genome integrity by cleaving retrotransposons and genome propagation by trapping mRNAs to form the germ plasm that instructs germ cell formation. The amino terminus of Aub (Aub-NT) is rich in arginines (Aub-NTRs), which are symmetrically dimethylated (sDMAs), and interacts with Tudor protein and other Tudor domain containing proteins (Tdrds). Aub-Tdrd interactions play critical roles in suppressing active retrotransposons via piRNA amplification and in germ plasm formation via generation of Aub-Tudor ribonucleoproteins. Here we show that Aub-NTRs are dispensable for primary piRNA biogenesis but essential for piRNA amplification and transposon control and that sDMAs in Aub-NT are essential for germ plasm formation and germ cell specification, but largely dispensable for piRNA amplification and transposon control.

2020-12-14 | GSE155874 | GEO

piRNA pathway targets active LINE1 elements to establish repressive H3K9me3 mark in germ cells

2014-06-13 | GSE58332 | GEO

piRNA pathway targets active LINE1 elements to establish repressive H3K9me3 mark in germ cells

Project description:Transposable elements (TEs) occupy large fraction of metazoan genomes and pose constant threat to genomic integrity. This threat is particularly critical in germ cells, as changes in the genome that are induced by TEs will be transmitted to the next generation. Small non-coding piwi interacting (pi)RNAs recognize and silence a diverse set of TEs in germ cells. In mice, piRNA-guided transposon repression correlates with establishment of CpG DNA methylation on their sequences, yet the mechanism and the spectrum of genomic targets of piRNA silencing are unknown. Here we show that in addition to DNA methylation, the piRNA pathway is required to maintain a high level of the repressive H3K9me3 histone modification on long interspersed nuclear elements (LINEs) in germ cells. piRNA-dependent chromatin repression targets exclusively full-length elements of actively transposing LINE families, demonstrating the remarkable ability of the piRNA pathway to recognize active elements among the large number of genomic transposon fragments. Total of 34 libraries were analyzed. In case of ChIP libraries, every 'input' sample was used for normalization of the respective ChIP (H3K9me3 or H3) sample; the input libraries preceed ChIP libraries in the list below. There are four replicates (input-ChIP pairs) for H3K9me3 ChIP on liver cells, two for ChIP on testicular somatic cells for each genotype (Miwi2 Het and KO); and four for ChIP on male germ cells for each genotype (one from FACS-sorted germ cells, and three from MACS-sorted germ cells). Each replicate has a Het/KO pair, and the respective libraries were cloned from the material isolated from littermates. One H3 ChIP for each genotype is included, with respective inputs.

2014-06-13 | E-GEOD-58332 | biostudies-arrayexpress

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