{"doi":"10.1101/2024.07.31.606086","title":"PROSER1 Modulates DNA Demethylation through Dual Mechanisms to Prevent Syndromic Developmental Malformations","abstract":"ABSTRACT The link between DNA methylation and neurodevelopmental disorders is well established. However, how DNA methylation is fine-tuned – ensuring precise gene expression and developmental fidelity – remains poorly understood. PROSER1, a known TET2 interactor, was recently linked to a severe neurodevelopmental disorder. Here, we demonstrate that PROSER1 interacts with all TET enzymes and stabilizes chromatin-bound T ET- O GT- P ROSER1- D BHS (TOPD) complexes, which regulate DNA demethylation and developmental gene expression. Surprisingly, we find that PROSER1 also sequesters TET enzymes, preventing widespread demethylation and transposable element de-repression. Our findings identify PROSER1 as a key factor which both positively and negatively regulates DNA demethylation essential for mammalian neurodevelopment.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2024,"id":501739,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9537,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1329311,"name":"Elena V. Knatko","orcid":null,"position":1,"is_corresponding":false},{"id":1328832,"name":"Xiang Li","orcid":"0000-0003-2757-0305","position":2,"is_corresponding":false},{"id":1212378,"name":"Ansgar Zoch","orcid":"0000-0003-2071-1590","position":3,"is_corresponding":false},{"id":1328833,"name":"Zoe Heckhausen","orcid":"0000-0003-0085-2492","position":4,"is_corresponding":false},{"id":563067,"name":"Stephanie Stransky","orcid":"0000-0003-0844-2754","position":5,"is_corresponding":false},{"id":1328834,"name":"Alejandro J. Brenes","orcid":"0000-0001-8298-2463","position":6,"is_corresponding":false},{"id":247704,"name":"Simone Sidoli","orcid":"0000-0001-9073-6641","position":7,"is_corresponding":false},{"id":257938,"name":"Petra Hájková","orcid":"0000-0003-4145-1468","position":8,"is_corresponding":false},{"id":260162,"name":"Dónal O’Carroll","orcid":"0000-0002-8626-2217","position":9,"is_corresponding":false},{"id":799977,"name":"K. Rasmussen","orcid":"0000-0002-7344-4177","position":10,"is_corresponding":false},{"id":1329310,"name":"Anna Fleming","orcid":null,"position":0,"is_corresponding":true}],"reference_count":55,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:10:15.999370Z","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":[]}