Bas van Steensel did got his PhD in 1995 from the University of Amsterdam. He had postdoc positions at the Rockefeller University (Titia de Lange lab) and the Fred Hutchinson Cancer Research Center (Steve Henikoff lab), studying various aspects of chromosome biology. Since 2002 he is Research Group Leader at the NKI. He is EMBO Member; recipient of an EURYI award, VICI and ERC Advanced grants; he is Extraordinary Professor at Erasmus University Medical Centre, Rotterdam.
RECOMB 2015 keynote talk: Mapping genome – nuclear lamina interactions in single cells
Mammalian interphase chromosomes interact with the nuclear lamina (NL) through hundreds of large Lamina Associated Domains (LADs). These interactions are thought to contribute to spatial genome organization. In addition, most genes in LADs are repressed, suggesting a role for NL contacts in gene regulation. The dynamics of LAD-NL interactions are poorly understood.
We previously developed a 'molecular contact memory' approach to track LADs in living cells. In each nucleus, only a subset of all LADs is 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 - at least in part - stochastically reshuffled.
We now report a modified version of our DamID method that can be used to map LAD-NL interactions genome-wide in single human cells. Analysis of more than 100 of these maps reveals a core architecture of gene-poor LADs that contact the NL with high cell-to-cell consistency, interspersed by LADs with more variable NL interactions. The single-cell maps indicate that NL contacts involve multivalent interactions over hundreds of kilobases. Strikingly, we observe extensive intra-chromosomal coordination of NL contacts, even over tens of megabases. Results of additional analyses of these datasets will be discussed.