title: Lamin A/C-promoter interactions specify chromatin state-dependent transcription outcomes.
abstract: The nuclear lamina is implicated in the organization of the eukaryotic nucleus. Association of nuclear lamins with the genome occurs through large chromatin domains including mostly, but not exclusively, repressed genes. How lamin interactions with regulatory elements modulate gene expression in different cellular contexts is unknown. We show here that in human adipose tissue stem cells, lamin A/C interacts with distinct spatially restricted subpromoter regions, both within and outside peripheral and intra-nuclear lamin-rich domains. These localized interactions are associated with distinct transcriptional outcomes in a manner dependent on local chromatin modifications. Down-regulation of lamin A/C leads to dissociation of lamin A/C from promoters and remodels repressive and permissive histone modifications by enhancing transcriptional permissiveness, but is not sufficient to elicit gene activation. Adipogenic differentiation resets a large number of lamin-genome associations globally and at subpromoter levels and redefines associated transcription outputs. We propose that lamin A/C acts as a modulator of local gene expression outcome through interaction with adjustable sites on promoters, and that these position-dependent transcriptional readouts may be reset upon differentiation.
authors.affiliation: Stem Cell Epigenetics Laboratory, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, and Norwegian Center for Stem Cell Research, Blindern, 0317 Oslo, Norway;
authors.forename: Eivind
authors.initials: E
authors.lastname: Lund
authors.forename: Anja R
authors.initials: AR
authors.lastname: Oldenburg
authors.forename: Erwan
authors.initials: E
authors.lastname: Delbarre
authors.forename: Christel T
authors.initials: CT
authors.lastname: Freberg
authors.forename: Isabelle
authors.initials: I
authors.lastname: Duband-Goulet
authors.forename: Ragnhild
authors.initials: R
authors.lastname: Eskeland
authors.forename: Brigitte
authors.initials: B
authors.lastname: Buendia
authors.forename: Philippe
authors.initials: P
authors.lastname: Collas
mesh_terms: D050156:Adipogenesis; D000273:Adipose Tissue / Q000166:cytology* / Q000378:metabolism; D002478:Cells, Cultured; D002843:Chromatin / Q000378:metabolism*; D020869:Gene Expression Profiling; D056426:Genetic Loci; D006801:Humans; D034904:Lamin Type A / Q000235:genetics / Q000378:metabolism*; D034881:Nuclear Lamina / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D014158:Transcription, Genetic; D015533:Transcriptional Activation
chemical_list: D002843:Chromatin; D034904:Lamin Type A; C440308:lamin C