Genome-wide Maps of Nuclear Lamina Interactions in Single Human Cells

TY - JOUR

T1 - Genome-wide Maps of Nuclear Lamina Interactions in Single Human Cells

AU - Kind, Jop

AU - Pagie, Ludo

AU - de Vries, Sandra S

AU - Nahidiazar, Leila

AU - Dey, Siddharth S

AU - Bienko, Magda

AU - Zhan, Ye

AU - Lajoie, Bryan

AU - de Graaf, Carolyn A

AU - Amendola, Mario

AU - Fudenberg, Geoffrey

AU - Imakaev, Maxim

AU - Mirny, Leonid A

AU - Jalink, Kees

AU - Dekker, Job

AU - van Oudenaarden, Alexander

AU - van Steensel, Bas

N1 - Copyright © 2015 Elsevier Inc. All rights reserved.

PY - 2015/9/24

Y1 - 2015/9/24

N2 - Mammalian interphase chromosomes interact with the nuclear lamina (NL) through hundreds of large lamina-associated domains (LADs). We report a method to map NL contacts genome-wide in single human cells. Analysis of nearly 400 maps reveals a core architecture consisting of gene-poor LADs that contact the NL with high cell-to-cell consistency, interspersed by LADs with more variable NL interactions. The variable contacts tend to be cell-type specific and are more sensitive to changes in genome ploidy than the consistent contacts. Single-cell maps indicate that NL contacts involve multivalent interactions over hundreds of kilobases. Moreover, we observe extensive intra-chromosomal coordination of NL contacts, even over tens of megabases. Such coordinated loci exhibit preferential interactions as detected by Hi-C. Finally, the consistency of NL contacts is inversely linked to gene activity in single cells and correlates positively with the heterochromatic histone modification H3K9me3. These results highlight fundamental principles of single-cell chromatin organization. VIDEO ABSTRACT.

AB - Mammalian interphase chromosomes interact with the nuclear lamina (NL) through hundreds of large lamina-associated domains (LADs). We report a method to map NL contacts genome-wide in single human cells. Analysis of nearly 400 maps reveals a core architecture consisting of gene-poor LADs that contact the NL with high cell-to-cell consistency, interspersed by LADs with more variable NL interactions. The variable contacts tend to be cell-type specific and are more sensitive to changes in genome ploidy than the consistent contacts. Single-cell maps indicate that NL contacts involve multivalent interactions over hundreds of kilobases. Moreover, we observe extensive intra-chromosomal coordination of NL contacts, even over tens of megabases. Such coordinated loci exhibit preferential interactions as detected by Hi-C. Finally, the consistency of NL contacts is inversely linked to gene activity in single cells and correlates positively with the heterochromatic histone modification H3K9me3. These results highlight fundamental principles of single-cell chromatin organization. VIDEO ABSTRACT.

U2 - 10.1016/j.cell.2015.08.040

DO - 10.1016/j.cell.2015.08.040

M3 - Article

C2 - 26365489

SN - 0092-8674

VL - 163

SP - 134

EP - 147

JO - Cell

JF - Cell

IS - 1

ER -