{"doi":"10.1101/gad.352120.124","title":"Transcriptional regulation of the piRNA pathway by Ovo in animal ovarian germ cells","abstract":"<jats:p>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<jats:italic>Drosophila</jats:italic>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<jats:italic>ovo</jats:italic>is repressed by<jats:italic>l(3)mbt</jats:italic>, 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.</jats:p>","journal":"Genes &amp; Development","year":2025,"id":613467,"datarank":0.3453877639491069,"base_score":2.302585092994046,"endowment":2.302585092994046,"self_citation_contribution":0.3453877639491069,"citation_network_contribution":0.0,"self_endowment_contribution":0.3453877639491069,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":9,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":11809,"name":"Gregory J. Hannon","orcid":"0000-0003-4021-3898","position":1,"is_corresponding":false},{"id":1370956,"name":"Benjamin Czech Nicholson","orcid":"0000-0001-8471-0007","position":2,"is_corresponding":false},{"id":713014,"name":"Azad Alizada","orcid":"0000-0002-2313-965X","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Transcriptional regulation of the piRNA pathway by Ovo in animal ovarian germ cells","abstract":"<jats:p>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<jats:italic>Drosophila</jats:italic>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<jats:italic>ovo</jats:italic>is repressed by<jats:italic>l(3)mbt</jats:italic>, 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.</jats:p>","is_dataset_classified":null,"base_score":2.302585092994046,"endowment":2.302585092994046,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"39797761","pmcid":"PMC11789646","openalex_id":"https://openalex.org/W4405674084","authors":[],"funders":[{"funder_name":"Cancer Research UK","grant_id":"G101107","title":null},{"funder_name":"Wellcome Trust","grant_id":"110161/Z/15/Z","title":null},{"funder_name":"Wellcome Trust","grant_id":"226627/Z/22/Z","title":null},{"funder_name":"Wellcome Trust","grant_id":"226627","title":"A small RNA-based immune system guards germ cell genomes"},{"funder_name":"Wellcome Trust","grant_id":"110161","title":"A small RNA based innate immune system guards germ cell genomes."}],"total_grants":5,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[{"year":2024,"count":1},{"year":2025,"count":4},{"year":2026,"count":4}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"http://genesdev.cshlp.org/content/early/2024/12/17/gad.352120.124.full.pdf","host_type":"journal"},{"url":"http://genesdev.cshlp.org/content/early/2024/12/17/gad.352120.124.full.pdf","host_type":"publisher"},{"url":"https://syndication.highwire.org/content/doi/10.1101/gad.352120.124","host_type":"publisher"},{"url":"https://doi.org/10.1101/gad.352120.124","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/39797761","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/11789646","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC11789646","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC11789646?pdf=render","host_type":"Europe_PMC"},{"url":"https://dx.doi.org/10.17863/cam.113515","host_type":""},{"url":"http://dx.doi.org/10.1101/gad.352120.124","host_type":""},{"url":"https://ora.ox.ac.uk/objects/uuid:b6ff5f64-36d5-4720-91df-02235c7fe3eb","host_type":""},{"url":"https://doi.org/10.17863/cam.113515","host_type":""},{"url":"https://www.repository.cam.ac.uk/handle/1810/376176","host_type":""}],"fields_of_study":["Chromosomal and Genetic Variations","Animal Genetics and Reproduction","Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities","0301 basic medicine","0303 health sciences","03 medical and health sciences","Animals","Female","RNA, Small Interfering","Ovary","Drosophila Proteins","Germ Cells","Gene Expression Regulation, Developmental","Drosophila melanogaster","Transcription Factors","Transcription, Genetic","Piwi-Interacting RNA"],"mesh_terms":["Piwi-Interacting RNA","Animals","DNA-Binding Proteins","Drosophila melanogaster","Female","Germ Cells","Male","Ovary","Transcription Factors","Transcription, Genetic","Gene Expression Regulation, Developmental","Drosophila Proteins","RNA, Small Interfering"],"keywords":["Piwi-interacting RNA","Biology","Germline","Transcription factor","In ovo","Genetics","Somatic cell","Ectopic expression","Regulation of gene expression","Gene","Cell biology","RNA","RNA interference","Embryo","Germ cells","Oogenesis","Transcriptional regulation","Pirnas","Transposon Silencing","Transcription, Genetic","Ovary","Gene Expression Regulation, Developmental","Research Papers","Drosophila melanogaster","Animals","Drosophila Proteins","Female","RNA, Small Interfering","Transcription Factors"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Life in Land"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"geo"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-02T08:13:20.498002Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}