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Cell. 2015 Sep 24;163(1):134-47. doi: 10.1016/j.cell.2015.08.040. Epub 2015 Sep 10.

Genome-wide maps of nuclear lamina interactions in single human cells.

Author information

1
Division of Gene Regulation, Netherlands Cancer Institute, Plesmanlaan 121, 1066CX Amsterdam, the Netherlands; Hubrecht Institute-KNAW (Royal Netherlands Academy of Arts and Sciences) and University Medical Center Utrecht, Cancer Genomics Netherlands, Uppsalalaan 8, 3584CT Utrecht, the Netherlands. Electronic address: j.kind@hubrecht.eu.
2
Division of Gene Regulation, Netherlands Cancer Institute, Plesmanlaan 121, 1066CX Amsterdam, the Netherlands.
3
Division of Cell Biology I, Netherlands Cancer Institute, Plesmanlaan 121, 1066CX Amsterdam, the Netherlands.
4
Hubrecht Institute-KNAW (Royal Netherlands Academy of Arts and Sciences) and University Medical Center Utrecht, Cancer Genomics Netherlands, Uppsalalaan 8, 3584CT Utrecht, the Netherlands.
5
Science for Life Laboratory, Division of Translational Medicine and Chemical Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, 171 21 Stockholm, Sweden.
6
Program in Systems Biology, Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605-0103, USA.
7
Graduate Program in Biophysics, Harvard University, Cambridge, MA 02138, USA.
8
Department of Physics, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
9
Department of Physics, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Institute for Medical Engineering and Science, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA.
10
Howard Hughes Medical Institute, Program in Systems Biology, Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605-0103, USA.
11
Division of Gene Regulation, Netherlands Cancer Institute, Plesmanlaan 121, 1066CX Amsterdam, the Netherlands. Electronic address: b.v.steensel@nki.nl.

Abstract

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.

PMID:
26365489
PMCID:
PMC4583798
DOI:
10.1016/j.cell.2015.08.040
[Indexed for MEDLINE]
Free PMC Article

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