title: Single-cell dynamics of genome-nuclear lamina interactions.
abstract: The nuclear lamina (NL) interacts with hundreds of large genomic regions termed lamina associated domains (LADs). The dynamics of these interactions and the relation to epigenetic modifications are poorly understood. We visualized the fate of LADs in single cells using a "molecular contact memory" approach. In each nucleus, only ~30% of LADs are positioned at the periphery; these LADs are in intermittent molecular contact with the NL but remain constrained to the periphery. Upon mitosis, LAD positioning is not detectably inherited but instead is stochastically reshuffled. Contact of individual LADs with the NL is linked to transcriptional repression and H3K9 dimethylation in single cells. Furthermore, we identify the H3K9 methyltransferase G9a as a regulator of NL contacts. Collectively, these results highlight principles of the dynamic spatial architecture of chromosomes in relation to gene regulation.
authors.affiliation: Division of Gene Regulation, Netherlands Cancer Institute, Amsterdam, 1066 CX, The Netherlands. j.kind@nki.nl
authors.forename: Jop
authors.initials: J
authors.lastname: Kind
authors.forename: Ludo
authors.initials: L
authors.lastname: Pagie
authors.forename: Havva
authors.initials: H
authors.lastname: Ortabozkoyun
authors.forename: Shelagh
authors.initials: S
authors.lastname: Boyle
authors.forename: Sandra S
authors.initials: SS
authors.lastname: de Vries
authors.forename: Hans
authors.initials: H
authors.lastname: Janssen
authors.forename: Mario
authors.initials: M
authors.lastname: Amendola
authors.forename: Leisha D
authors.initials: LD
authors.lastname: Nolen
authors.forename: Wendy A
authors.initials: WA
authors.lastname: Bickmore
authors.forename: Bas
authors.initials: B
authors.lastname: van Steensel
mesh_terms: D000225:Adenine / Q000378:metabolism; D045744:Cell Line, Tumor; D002875:Chromosomes / Q000378:metabolism*; D019175:DNA Methylation; D005786:Gene Expression Regulation; D016678:Genome; D006570:Heterochromatin / Q000378:metabolism; D006649:Histocompatibility Antigens / Q000378:metabolism; D011495:Histone-Lysine N-Methyltransferase / Q000378:metabolism; D006801:Humans; D008938:Mitosis; D034881:Nuclear Lamina / Q000737:chemistry* / Q000378:metabolism; D059010:Single-Cell Analysis / Q000379:methods*
chemical_list: D006570:Heterochromatin; D006649:Histocompatibility Antigens; C445405:EHMT2 protein, human; D011495:Histone-Lysine N-Methyltransferase; D000225:Adenine