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Mol Cell. 2016 Feb 4;61(3):461-473. doi: 10.1016/j.molcel.2016.01.001. Epub 2016 Jan 28.

Cause and Consequence of Tethering a SubTAD to Different Nuclear Compartments.

Author information

1
Hubrecht Institute-KNAW & University Medical Center Utrecht, Uppsalalaan 8, 3584 CT Utrecht, the Netherlands.
2
Synthetic Systems Biology and Nuclear Organization Group, Swammerdam Institute for Life Sciences, University of Amsterdam, 1098 XH Amsterdam, the Netherlands.
3
Hubrecht Institute-KNAW & University Medical Center Utrecht, Uppsalalaan 8, 3584 CT Utrecht, the Netherlands. Electronic address: w.delaat@hubrecht.eu.

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.

PMID:
26833089
PMCID:
PMC4747903
DOI:
10.1016/j.molcel.2016.01.001
[Indexed for MEDLINE]
Free PMC Article

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