{"doi":"10.1126/sciadv.adr2299","title":"Transcriptional coupling of telomeric retrotransposons with the cell cycle","abstract":"Unlike most species that use telomerase for telomere maintenance, many dipterans, including Drosophila , rely on three telomere-specific retrotransposons (TRs)— HeT-A , TART , and TAHRE —to form tandem repeats at chromosome ends. Although TR transcription is crucial in their life cycle, its regulation remains poorly understood. This study identifies the Mediator complex, E2F1-Dp, and Scalloped/dTEAD as key regulators of TR transcription. Reducing the activity of the Mediator or Sd/dTEAD increases TR expression and telomere length, while overexpressing E2F1-Dp or depleting Rbf1 stimulates TR transcription. The Mediator and Sd/dTEAD regulate this process through E2F1-Dp. CUT&RUN (Cleavage under targets and release using nuclease) analysis shows direct binding of CDK8, Dp, and Sd/dTEAD to telomeric repeats, with motif enrichment revealing E2F- and TEAD-binding sites. These findings uncover the Mediator complex’s role in controlling TR transcription and telomere length through E2F1-Dp and Sd, coupling the transcriptional regulation of the TR life cycle with host cell-cycle machinery to protect chromosome ends in Drosophila .","journal":"Science Advances","year":2025,"id":537805,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9568,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":385794,"name":"Xiaojun Xie","orcid":"0000-0001-7768-1586","position":1,"is_corresponding":false},{"id":899938,"name":"Xiao Li","orcid":"0000-0002-9682-5335","position":2,"is_corresponding":false},{"id":369438,"name":"Xingjie Ren","orcid":"0000-0002-2348-4162","position":3,"is_corresponding":false},{"id":1322811,"name":"Jasmine L. Sun","orcid":null,"position":4,"is_corresponding":false},{"id":135946,"name":"Zhen Lin","orcid":"0000-0002-9229-053X","position":5,"is_corresponding":false},{"id":369440,"name":"Rajitha-Udakara-Sampath Hemba-Waduge","orcid":"0000-0002-4931-5818","position":6,"is_corresponding":false},{"id":369444,"name":"Jun‐Yuan Ji","orcid":"0000-0002-4483-4336","position":7,"is_corresponding":false},{"id":1260908,"name":"Mengmeng Liu","orcid":"0009-0006-9644-5099","position":0,"is_corresponding":true}],"reference_count":97,"raw_metadata":null,"created_at":"2026-07-19T02:52:16.891390Z","pmid":"39752503","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":[]}