title: Prepatterning of differentiation-driven nuclear lamin A/C-associated chromatin domains by GlcNAcylated histone H2B.
abstract: Dynamic interactions of nuclear lamins with chromatin through lamin-associated domains (LADs) contribute to spatial arrangement of the genome. Here, we provide evidence for prepatterning of differentiation-driven formation of lamin A/C LADs by domains of histone H2B modified on serine 112 by the nutrient sensor O-linked N-acetylglucosamine (H2BS112GlcNAc), which we term GADs. We demonstrate a two-step process of lamin A/C LAD formation during in vitro adipogenesis, involving spreading of lamin A/C-chromatin interactions in the transition from progenitor cell proliferation to cell-cycle arrest, and genome-scale redistribution of these interactions through a process of LAD exchange within hours of adipogenic induction. Lamin A/C LADs are found both in active and repressive chromatin contexts that can be influenced by cell differentiation status. De novo formation of adipogenic lamin A/C LADs occurs nonrandomly on GADs, which consist of megabase-size intergenic and repressive chromatin domains. Accordingly, whereas predifferentiation lamin A/C LADs are gene-rich, post-differentiation LADs harbor repressive features reminiscent of lamin B1 LADs. Release of lamin A/C from genes directly involved in glycolysis concurs with their transcriptional up-regulation after adipogenic induction, and with downstream elevations in H2BS112GlcNAc levels and O-GlcNAc cycling. Our results unveil an epigenetic prepatterning of adipogenic LADs by GADs, suggesting a coupling of developmentally regulated lamin A/C-genome interactions to a metabolically sensitive chromatin modification.
authors.affiliation: Department of Molecular Medicine, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, 0317 Oslo, Norway;
authors.forename: Torunn
authors.initials: T
authors.lastname: Rønningen
authors.affiliation: Department of Molecular Medicine, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, 0317 Oslo, Norway;
authors.forename: Akshay
authors.initials: A
authors.lastname: Shah
authors.affiliation: Department of Molecular Medicine, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, 0317 Oslo, Norway; Norwegian Center for Stem Cell Research, Oslo University Hospital, 0317 Oslo, Norway.
authors.forename: Anja R
authors.initials: AR
authors.lastname: Oldenburg
authors.affiliation: Department of Molecular Medicine, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, 0317 Oslo, Norway;
authors.forename: Kristin
authors.initials: K
authors.lastname: Vekterud
authors.affiliation: Department of Molecular Medicine, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, 0317 Oslo, Norway;
authors.forename: Erwan
authors.initials: E
authors.lastname: Delbarre
authors.affiliation: Department of Molecular Medicine, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, 0317 Oslo, Norway; Norwegian Center for Stem Cell Research, Oslo University Hospital, 0317 Oslo, Norway.
authors.forename: Jan Øivind
authors.initials: JØ
authors.lastname: Moskaug
authors.affiliation: Department of Molecular Medicine, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, 0317 Oslo, Norway; Norwegian Center for Stem Cell Research, Oslo University Hospital, 0317 Oslo, Norway.
authors.forename: Philippe
authors.initials: P
authors.lastname: Collas
mesh_terms: D000107:Acetylation; D050156:Adipogenesis; D002454:Cell Differentiation; D002843:Chromatin / Q000235:genetics / Q000378:metabolism*; D042002:Chromatin Assembly and Disassembly; D047369:Chromatin Immunoprecipitation; D005786:Gene Expression Regulation; D006019:Glycolysis / Q000235:genetics; D006031:Glycosylation; D059014:High-Throughput Nucleotide Sequencing; D006657:Histones / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D034904:Lamin Type A / Q000378:metabolism*; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs
chemical_list: D002843:Chromatin; D006657:Histones; D034904:Lamin Type A