C19ORF84 connects piRNA and DNA methylation machineries to defend the mammalian germline
Ontology highlight
ABSTRACT:
PROVIDER: PRJEB51968 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| ERR9435400_1.fastq.gz | Fastqsanger.gz | |||
| ERR9435400_2.fastq.gz | Fastqsanger.gz | |||
| ERR9435410_1.fastq.gz | Fastqsanger.gz | |||
| ERR9435410_2.fastq.gz | Fastqsanger.gz | |||
| ERR9435401_1.fastq.gz | Fastqsanger.gz |
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Similar Datasets
Project description:C19ORF84 connects piRNA and DNA methylation machineries to defend the mammalian germ line
| PRJNA818177 | ENA
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
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
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
Project description: Not available
| S-EPMC10960678 | biostudies-literature
Project description:The gene-regulatory mechanisms controlling the expression of the germline PIWI-interacting RNA (piRNA) pathway components within the gonads of metazoan species remain largely unexplored. In contrast to the male germline piRNA pathway, which in mice is known to be activated by the testis-specific transcription factor A-MYB, the nature of the ovary-specific gene-regulatory network driving the female germline piRNA pathway remains a mystery. Here, using Drosophila as a model, we combined multiple genomics approaches to reveal the transcription factor Ovo as regulator of the germline piRNA pathway in ovarian germ cells. Ectopic expression of Ovo in ovarian somatic cells activates germline piRNA pathway components, including the ping-pong factors Aubergine, Argonaute-3, and Vasa, leading to assembly of perinuclear cellular structures resembling nuage bodies of germ cells. We found that in ovarian somatic cells, transcription of ovo is repressed by l(3)mbt, thus preventing expression of germline piRNA pathway genes in the soma. Cross-species ChIP-seq and motif analyses demonstrate that Ovo is binding to genomic CCGTTA motifs within the promoters of germline piRNA pathway genes, suggesting a regulation by Ovo in ovaries analogous to that of A-MYB in testes. Our results also show consistent engagement of the Ovo transcription factor family at ovarian piRNA clusters across metazoan species, reflecting a deep evolutionary conservation of this regulatory paradigm from insects to humans.
2024-12-23 | GSE233246 | GEO
Project description:PIWI-interacting RNAs (piRNAs), a class of small RNAs that guide transposon silencing in animals, are processed in the cytoplasm from RNA Polymerase II transcripts. How piRNA precursors, which often lack RNA maturation signatures and thereby violate quality control checkpoints, achieve nuclear export is unknown. Here, we uncover a germline-specific RNA export pathway in Drosophila, that escorts piRNA precursors from their heterochromatic origins to nuage, the cytoplasmic piRNA processing centres. This pathway connects canonical nuclear export factors—the RNA helicase UAP56, the NXF cofactor Nxt1/p15, and the exportin Crm1/Xpo1—with Nxf3, a variant of the mRNA exporter Nxf1/Tap. Nxf3 recruitment to nascent piRNA precursors occurs via the heterochromatin protein 1-variant Rhino and CG13741/Bootlegger, a new piRNA pathway factor, thereby making piRNA precursor export independent of RNA processing events. Thus, similar to retroviral hijacking of cellular export factors, piRNA precursor export evolved to bend canonical gene expression rules through bypassing nuclear RNA surveillance mechanisms.
2019-03-29 | PXD012717 | Pride
Project description:In mice, the PIWI-piRNA pathway is essential to re-establish transposon silencing during male germline reprogramming. The cytoplasmic PIWI protein MILI mediates piRNA-guided transposon RNA cleavage as well as piRNA amplification. MIWI2-bound piRNAs and its nuclear localization are proposed to be dependent upon MILI function. Here, we demonstrate the existence of a piRNA biogenesis pathway that in the absence of MILI that sustains partial MIWI2 function and reprogramming activity.
2017-04-25 | E-MTAB-5561 | biostudies-arrayexpress
Project description:Piwi-interacting RNAs (piRNAs) control transposable element (TE) activity in the germline. piRNAs are produced from single-stranded precursors transcribed from distinct genomic loci, enriched by TE fragments and termed piRNA clusters. The specific chromatin organization and transcriptional regulation of Drosophila germline-specific piRNA clusters ensure transcription and processing of piRNA precursors. TEs harbour various regulatory elements that could affect piRNA cluster integrity. One of such elements is the suppressor-of-hairy-wing (Su(Hw))-mediated insulator, which is harboured in the retrotransposon gypsy. To understand how insulators contribute to piRNA cluster activity, we studied the effects of transgenes containing gypsy insulators on local organization of endogenous piRNA clusters. We show that transgene insertions interfere with piRNA precursor transcription, small RNA production and the formation of piRNA cluster-specific chromatin, a hallmark of which is Rhino, the germline homolog of the heterochromatin protein 1 (HP1). The mutations of Su(Hw) restored the integrity of piRNA clusters in transgenic strains. Surprisingly, Su(Hw) depletion enhanced the production of piRNAs by the domesticated telomeric retrotransposon TART, indicating that Su(Hw)-dependent elements protect TART transcripts from piRNA processing machinery in telomeres. A genome-wide analysis revealed that Su(Hw)-binding sites are depleted in endogenous germline piRNA clusters, suggesting that their functional integrity is under strict evolutionary constraints.
2019-03-15 | GSE125173 | GEO
Project description:The gene-regulatory mechanisms behind the female germline piRNA pathway in ovaries of metazoan species remain largely unexplored. Here, using the Drosophila model and combinations of RNA-seq, ATAC-seq, and single-cell approaches, we reveal the transcription factors that regulate the female germline piRNA pathway in animal ovaries.
2024-12-23 | GSE233245 | GEO