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The lipodystrophy-associated LMNA p.R482W mutation is known to impair adipogenic differentiation, but the mechanisms involved are unclear. We show in this study that the lamin A p.R482W hot spot mutation prevents adipogenic gene expression by epigenetically deregulating long-range enhancers of the anti-adipogenic MIR335 microRNA gene in human adipocyte progenitor cells. The R482W mutation results in a loss of function of differentiation-dependent lamin A binding to the MIR335 locus. This impairs H3K27 methylation and instead favors H3K27 acetylation on MIR335 enhancers. The lamin A mutation further promotes spatial clustering of MIR335 enhancer and promoter elements along with overexpression of the MIR355 gene after adipogenic induction. Our results link a laminopathy-causing lamin A mutation to an unsuspected deregulation of chromatin states and spatial conformation of an miRNA locus critical for adipose progenitor cell fate.<\/jats:p>","DOI":"10.1083\/jcb.201701043","type":"journal-article","created":{"date-parts":[[2017,7,27]],"date-time":"2017-07-27T15:15:38Z","timestamp":1501168538000},"page":"2731-2743","update-policy":"https:\/\/doi.org\/10.1083\/jcb.crossmarkpolicy","source":"Crossref","is-referenced-by-count":82,"title":["A lipodystrophy-causing lamin A mutant alters conformation and epigenetic regulation of the anti-adipogenic <i>MIR335<\/i> locus"],"prefix":"10.1083","volume":"216","author":[{"given":"Anja","family":"Oldenburg","sequence":"first","affiliation":[{"name":"Department of Molecular Medicine, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Oslo, Norway 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nolwenn","family":"Briand","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Oslo, Norway 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anita L.","family":"S\u00f8rensen","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Oslo, Norway 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inswasti","family":"Cahyani","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Oslo, Norway 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akshay","family":"Shah","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Oslo, Norway 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan \u00d8ivind","family":"Moskaug","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Oslo, Norway 1"},{"name":"Norwegian Center for Stem Cell Research, Department of Immunology, Oslo University Hospital, Oslo, Norway 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5059-6901","authenticated-orcid":true,"given":"Philippe","family":"Collas","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Oslo, Norway 1"},{"name":"Norwegian Center for Stem Cell Research, Department of Immunology, Oslo University Hospital, Oslo, Norway 2"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2017,7,27]]},"reference":[{"key":"2023072314512030700_bib1","doi-asserted-by":"publisher","first-page":"653","DOI":"10.1093\/hmg\/ddi480","article-title":"Nuclear lamin A inhibits adipocyte differentiation: implications for Dunnigan-type familial partial lipodystrophy","volume":"15","author":"Boguslavsky","year":"2006","journal-title":"Hum. 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