{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Generoso SF"],"funding":["HHS | National Institutes of Health","spanish ministry of science and innovation","HHS | NIH | Office of Extramural Research, National Institutes of Health","NIDDK NIH HHS","NIMH NIH HHS","NIGMS NIH HHS"],"pagination":["e2213810120"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9942853"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["120(4)"],"pubmed_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 of the United States of America"],"pubmed_title":["Cohesin controls X chromosome structure remodeling and X-reactivation during mouse iPSC-reprogramming."],"pmcid":["PMC9942853"],"funding_grant_id":["R01-GM58839","BFU2014-55275-P","R01 MH118351","R01 GM058839","R01-MH118351","R35 GM137916","P30 DK040561"],"pubmed_authors":["Cosma MP","Neguembor MV","Sadreyev RI","Audergon P","Payer B","Yabuta Y","Hochedlinger K","Ricci R","Beliveau BJ","Saitou M","Bauer M","Lee JT","Hershberg EA","Generoso SF","Kurimoto K"],"additional_accession":[]},"is_claimable":false,"name":"Cohesin controls X chromosome structure remodeling and X-reactivation during mouse iPSC-reprogramming.","description":"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.","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 Jan","modification":"2025-05-18T12:58:01.214Z","creation":"2025-05-18T12:58:01.214Z"},"accession":"S-EPMC9942853","cross_references":{"pubmed":["36669113"],"doi":["10.1073/pnas.2213810120"]}}