{"doi":"10.1073/pnas.2213810120","title":"Cohesin controls X chromosome structure remodeling and X-reactivation during mouse iPSC-reprogramming","abstract":"Reactivation of the inactive X chromosome is a hallmark epigenetic event during reprogramming of mouse female somatic cells to induced pluripotent stem cells (iPSCs). This involves global structural remodeling from a condensed, heterochromatic into an open, euchromatic state, thereby changing a transcriptionally inactive into an active chromosome. Despite recent advances, very little is currently known about the molecular players mediating this process and how this relates to iPSC-reprogramming in general. To gain more insight, here we perform a RNAi-based knockdown screen during iPSC-reprogramming of mouse fibroblasts. We discover factors important for X chromosome reactivation (XCR) and iPSC-reprogramming. Among those, we identify the cohesin complex member SMC1a as a key molecule with a specific function in XCR, as its knockdown greatly affects XCR without interfering with iPSC-reprogramming. Using super-resolution microscopy, we find SMC1a to be preferentially enriched on the active compared with the inactive X chromosome and that SMC1a is critical for the decompacted state of the active X. Specifically, depletion of SMC1a leads to contraction of the active X both in differentiated and in pluripotent cells, where it normally is in its most open state. In summary, we reveal cohesin as a key factor for remodeling of the X chromosome from an inactive to an active structure and that this is a critical step for XCR during iPSC-reprogramming.","journal":"Proceedings of the National Academy of Sciences","year":2023,"id":357564,"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":12,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9471,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":633929,"name":"Maria Victoria Neguembor","orcid":"0000-0002-1583-1304","position":1,"is_corresponding":false},{"id":258051,"name":"Elliot A. Hershberg","orcid":"0000-0003-2068-3366","position":2,"is_corresponding":false},{"id":260528,"name":"Ruslan I. Sadreyev","orcid":"0000-0002-4240-5466","position":3,"is_corresponding":false},{"id":1107363,"name":"Kazuki Kurimoto","orcid":"0000-0003-0206-414X","position":4,"is_corresponding":false},{"id":889622,"name":"Yukihiro Yabuta","orcid":"0000-0002-6437-1201","position":5,"is_corresponding":false},{"id":1107852,"name":"Raffaele Ricci","orcid":null,"position":6,"is_corresponding":false},{"id":30107,"name":"Pauline Audergon","orcid":"0000-0002-1624-7388","position":7,"is_corresponding":false},{"id":651827,"name":"Moritz Bauer","orcid":"0000-0002-5937-8169","position":8,"is_corresponding":false},{"id":889634,"name":"Mitinori Saitou","orcid":"0000-0002-2895-6798","position":9,"is_corresponding":false},{"id":56485,"name":"Konrad Hochedlinger","orcid":"0000-0001-5811-5386","position":10,"is_corresponding":false},{"id":21366,"name":"Brian J. Beliveau","orcid":"0000-0003-1314-3118","position":11,"is_corresponding":false},{"id":477253,"name":"Maria Pia Cosma","orcid":"0000-0003-4207-5097","position":12,"is_corresponding":false},{"id":208747,"name":"Jeannie T. Lee","orcid":"0000-0001-7786-8850","position":13,"is_corresponding":false},{"id":651830,"name":"Bernhard Payer","orcid":"0000-0002-4694-2082","position":14,"is_corresponding":false},{"id":1107362,"name":"Serena Generoso","orcid":"0000-0002-2733-1710","position":0,"is_corresponding":true}],"reference_count":84,"raw_metadata":null,"created_at":"2026-07-19T01:13:39.186262Z","pmid":"36669113","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":[]}