title: Loss of lamin A function increases chromatin dynamics in the nuclear interior.
abstract: Chromatin is organized in a highly ordered yet dynamic manner in the cell nucleus, but the principles governing this organization remain unclear. Similarly, it is unknown whether, and how, various proteins regulate chromatin motion and as a result influence nuclear organization. Here by studying the dynamics of different genomic regions in the nucleus of live cells, we show that the genome has highly constrained dynamics. Interestingly, depletion of lamin A strikingly alters genome dynamics, inducing a dramatic transition from slow anomalous diffusion to fast and normal diffusion. In contrast, depletion of LAP2α, a protein that interacts with lamin A and chromatin, has no such effect on genome dynamics. We speculate that chromosomal inter-chain interactions formed by lamin A throughout the nucleus contribute to chromatin dynamics, and suggest that the molecular regulation of chromatin diffusion by lamin A in the nuclear interior is critical for the maintenance of genome organization.
authors: Physics Department and Nanotechnology Institute, Bar Ilan University, Ramat Gan 5290002, Israel.|The Mina &Everard Goodman Faculty of Life Sciences and Nanotechnology Institute, Bar Ilan University, Ramat Gan 5290002, Israel.
authors: I
authors: I
authors: Bronshtein
authors: Physics Department and Nanotechnology Institute, Bar Ilan University, Ramat Gan 5290002, Israel.
authors: E
authors: E
authors: Kepten
authors: Physics Department and Nanotechnology Institute, Bar Ilan University, Ramat Gan 5290002, Israel.
authors: I
authors: I
authors: Kanter
authors: Physics Department and Nanotechnology Institute, Bar Ilan University, Ramat Gan 5290002, Israel.
authors: S
authors: S
authors: Berezin
authors: Physics Department and Nanotechnology Institute, Bar Ilan University, Ramat Gan 5290002, Israel.
authors: M
authors: M
authors: Lindner
authors: Edward A. Doisy Department of Biochemistry and Molecular Biology, School of Medicine, St Louis University, 1100 South Grand Ave. St Louis, Missouri 63104, USA.
authors: Abena B
authors: AB
authors: Redwood
authors: Manitoba Institute of Cell Biology, Department of Physiology and Pathophysiology, University of Manitoba, Cancer Care Manitoba, Winnipeg, Manitoba, Canada R3E 0V9.
authors: S
authors: S
authors: Mai
authors: Edward A. Doisy Department of Biochemistry and Molecular Biology, School of Medicine, St Louis University, 1100 South Grand Ave. St Louis, Missouri 63104, USA.
authors: S
authors: http://orcid.org/0000-0001-9631-1206
authors: S
authors: Gonzalo
authors: Max F. Perutz Laboratories, Medical University Vienna, Vienna Biocenter (VBC), Dr. Bohr-Gasse 9, 1030 Vienna, Austria.
authors: R
authors: R
authors: Foisner
authors: The Mina &Everard Goodman Faculty of Life Sciences and Nanotechnology Institute, Bar Ilan University, Ramat Gan 5290002, Israel.
authors: Y
authors: Y
authors: Shav-Tal
authors: Physics Department and Nanotechnology Institute, Bar Ilan University, Ramat Gan 5290002, Israel.
authors: Y
authors: Y
authors: Garini
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002843:Chromatin / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000378:metabolism; D006801:Humans; D034904:Lamin Type A / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D041681:NIH 3T3 Cells; D034622:RNA Interference / Q000502:physiology*; D034741:RNA, Small Interfering; D016615:Telomere
chemical_list: D002843:Chromatin; D004268:DNA-Binding Proteins; D034904:Lamin Type A; D008565:Membrane Proteins; D034741:RNA, Small Interfering; C093413:lamina-associated polypeptide 2