Cause and Consequence of Tethering a SubTAD to Different Nuclear Compartments

TY - JOUR

T1 - Cause and Consequence of Tethering a SubTAD to Different Nuclear Compartments

AU - Wijchers, Patrick J

AU - Krijger, Peter H L

AU - Geeven, Geert

AU - Zhu, Yun

AU - Denker, Annette

AU - Verstegen, Marjon J A M

AU - Valdes-Quezada, Christian

AU - Vermeulen, Carlo

AU - Janssen, Mark

AU - Teunissen, Hans

AU - Anink-Groenen, Lisette C M

AU - Verschure, Pernette J

AU - de Laat, Wouter

N1 - Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

PY - 2016/2/4

Y1 - 2016/2/4

N2 - 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.

AB - 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.

KW - Animals

KW - Cell Nucleus

KW - Cells, Cultured

KW - Chromatin

KW - Chromatin Assembly and Disassembly

KW - Chromosome Segregation

KW - Embryonic Stem Cells

KW - Gene Expression Regulation

KW - Genetic Loci

KW - Homeodomain Proteins

KW - Lac Operon

KW - Lac Repressors

KW - Methyltransferases

KW - Mice, 129 Strain

KW - Mice, Inbred C57BL

KW - Polycomb Repressive Complex 2

KW - Repressor Proteins

KW - Transfection

U2 - 10.1016/j.molcel.2016.01.001

DO - 10.1016/j.molcel.2016.01.001

M3 - Article

C2 - 26833089

SN - 1097-2765

VL - 61

SP - 461

EP - 473

JO - Molecular Cell

JF - Molecular Cell

IS - 3

ER -