Prepatterning of differentiation-driven nuclear lamin A/C-associated chromatin domains by GlcNAcylated histone H2B

Genome Res. 2015 Dec;25(12):1825-35. doi: 10.1101/gr.193748.115. Epub 2015 Sep 10.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Adipogenesis
  • Cell Differentiation*
  • Chromatin / genetics
  • Chromatin / metabolism*
  • Chromatin Assembly and Disassembly
  • Chromatin Immunoprecipitation
  • Gene Expression Regulation
  • Glycolysis / genetics
  • Glycosylation
  • High-Throughput Nucleotide Sequencing
  • Histones / chemistry
  • Histones / metabolism*
  • Humans
  • Lamin Type A / metabolism*
  • Protein Binding
  • Protein Interaction Domains and Motifs


  • Chromatin
  • Histones
  • Lamin Type A

Associated data

  • GEO/GSE63346