Cause and Consequence of Tethering a SubTAD to Different Nuclear Compartments

Patrick J Wijchers, Peter H L Krijger, Geert Geeven, Yun Zhu, Annette Denker, Marjon J A M Verstegen, Christian Valdes-Quezada, Carlo Vermeulen, Mark Janssen, Hans Teunissen, Lisette C M Anink-Groenen, Pernette J Verschure, Wouter de Laat

Research output: Contribution to journal/periodicalArticleScientificpeer-review

Abstract

Detailed genomic contact maps have revealed that chromosomes are structurally organized in megabase-sized topologically associated domains (TADs) that encompass smaller subTADs. These domains segregate in the nuclear space to form active and inactive nuclear compartments, but cause and consequence of compartmentalization are largely unknown. Here, we combined lacO/lacR binding platforms with allele-specific 4C technologies to track their precise position in the three-dimensional genome upon recruitment of NANOG, SUV39H1, or EZH2. We observed locked genomic loci resistant to spatial repositioning and unlocked loci that could be repositioned to different nuclear subcompartments with distinct chromatin signatures. Focal protein recruitment caused the entire subTAD, but not surrounding regions, to engage in new genomic contacts. Compartment switching was found uncoupled from transcription changes, and the enzymatic modification of histones per se was insufficient for repositioning. Collectively, this suggests that trans-associated factors influence three-dimensional compartmentalization independent of their cis effect on local chromatin composition and activity.

Original languageEnglish
Pages (from-to)461-73
Number of pages13
JournalMolecular Cell
Volume61
Issue number3
DOIs
Publication statusPublished - 04 Feb 2016

Keywords

  • Animals
  • Cell Nucleus
  • Cells, Cultured
  • Chromatin
  • Chromatin Assembly and Disassembly
  • Chromosome Segregation
  • Embryonic Stem Cells
  • Gene Expression Regulation
  • Genetic Loci
  • Homeodomain Proteins
  • Lac Operon
  • Lac Repressors
  • Methyltransferases
  • Mice, 129 Strain
  • Mice, Inbred C57BL
  • Polycomb Repressive Complex 2
  • Repressor Proteins
  • Transfection

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