title: Genome-wide maps of nuclear lamina interactions in single human cells.
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.
authors.affiliation: 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.
authors.forename: Jop
authors.initials: J
authors.lastname: Kind
authors.affiliation: Division of Gene Regulation, Netherlands Cancer Institute, Plesmanlaan 121, 1066CX Amsterdam, the Netherlands.
authors.forename: Ludo
authors.initials: L
authors.lastname: Pagie
authors.affiliation: Division of Gene Regulation, Netherlands Cancer Institute, Plesmanlaan 121, 1066CX Amsterdam, the Netherlands.
authors.forename: Sandra S
authors.initials: SS
authors.lastname: de Vries
authors.affiliation: Division of Cell Biology I, Netherlands Cancer Institute, Plesmanlaan 121, 1066CX Amsterdam, the Netherlands.
authors.forename: Leila
authors.initials: L
authors.lastname: Nahidiazar
authors.affiliation: Hubrecht Institute-KNAW (Royal Netherlands Academy of Arts and Sciences) and University Medical Center Utrecht, Cancer Genomics Netherlands, Uppsalalaan 8, 3584CT Utrecht, the Netherlands.
authors.forename: Siddharth S
authors.initials: SS
authors.lastname: Dey
authors.affiliation: Science for Life Laboratory, Division of Translational Medicine and Chemical Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, 171 21 Stockholm, Sweden.
authors.forename: Magda
authors.initials: M
authors.lastname: Bienko
authors.affiliation: Program in Systems Biology, Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605-0103, USA.
authors.forename: Ye
authors.initials: Y
authors.lastname: Zhan
authors.affiliation: Program in Systems Biology, Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605-0103, USA.
authors.forename: Bryan
authors.initials: B
authors.lastname: Lajoie
authors.affiliation: Division of Gene Regulation, Netherlands Cancer Institute, Plesmanlaan 121, 1066CX Amsterdam, the Netherlands.
authors.forename: Carolyn A
authors.initials: CA
authors.lastname: de Graaf
authors.affiliation: Division of Gene Regulation, Netherlands Cancer Institute, Plesmanlaan 121, 1066CX Amsterdam, the Netherlands.
authors.forename: Mario
authors.initials: M
authors.lastname: Amendola
authors.affiliation: Graduate Program in Biophysics, Harvard University, Cambridge, MA 02138, USA.
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Fudenberg
authors.affiliation: Department of Physics, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Maxim
authors.initials: M
authors.lastname: Imakaev
authors.affiliation: 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.
authors.forename: Leonid A
authors.initials: LA
authors.lastname: Mirny
authors.affiliation: Division of Cell Biology I, Netherlands Cancer Institute, Plesmanlaan 121, 1066CX Amsterdam, the Netherlands.
authors.forename: Kees
authors.initials: K
authors.lastname: Jalink
authors.affiliation: Howard Hughes Medical Institute, Program in Systems Biology, Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605-0103, USA.
authors.forename: Job
authors.initials: J
authors.lastname: Dekker
authors.affiliation: Hubrecht Institute-KNAW (Royal Netherlands Academy of Arts and Sciences) and University Medical Center Utrecht, Cancer Genomics Netherlands, Uppsalalaan 8, 3584CT Utrecht, the Netherlands.
authors.forename: Alexander
authors.initials: A
authors.lastname: van Oudenaarden
authors.affiliation: Division of Gene Regulation, Netherlands Cancer Institute, Plesmanlaan 121, 1066CX Amsterdam, the Netherlands. Electronic address: b.v.steensel@nki.nl.
authors.forename: Bas
authors.initials: B
authors.lastname: van Steensel
mesh_terms: D045744:Cell Line, Tumor; D002843:Chromatin / Q000737:chemistry / Q000378:metabolism*; D002875:Chromosomes / Q000737:chemistry / Q000378:metabolism; D055106:Genome-Wide Association Study; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007399:Interphase; D034881:Nuclear Lamina / Q000378:metabolism*; D059010:Single-Cell Analysis / Q000379:methods*
chemical_list: D002843:Chromatin