Molecular Maps of the Reorganization of Genome-Nuclear Lamina Interactions during Differentiation

Daan Peric-Hupkes, Wouter Meuleman, Ludo Pagie, Sophia W. M. Bruggeman, Irina Solovei, Wim Brugman, Stefan Graef, Paul Flicek, Ron M. Kerkhoven, Maarten van Lohuizen, Marcel Reinders, Lodewyk Wessels, Bas van Steensel*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

611 Citations (Scopus)

Abstract

The three-dimensional organization of chromosomes within the nucleus and its dynamics during differentiation are largely unknown. To visualize this process in molecular detail, we generated high-resolution maps of genome-nuclear lamina interactions during subsequent differentiation of mouse embryonic stem cells via lineage-committed neural precursor cells into terminally differentiated astrocytes. This reveals that a basal chromosome architecture present in embryonic stem cells is cumulatively altered at hundreds of sites during lineage commitment and subsequent terminal differentiation. This remodeling involves both individual transcription units and multigene regions and affects many genes that determine cellular identity. Often, genes that move away from the lamina are concomitantly activated; many others, however, remain inactive yet become unlocked for activation in a next differentiation step. These results suggest that lamina-genome interactions are widely involved in the control of gene expression programs during lineage commitment and terminal differentiation.

Original languageEnglish
Pages (from-to)603-613
Number of pages11
JournalMolecular Cell
Volume38
Issue number4
DOIs
Publication statusPublished - 28-May-2010
Externally publishedYes

Keywords

  • EMBRYONIC STEM-CELLS
  • GENE-REGULATION
  • RNA-POLYMERASE
  • PLURIPOTENT
  • TRANSCRIPTION
  • METHYLATION
  • INDUCTION
  • ORGANIZATION
  • REPRESSION
  • LANGUAGE

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