HMGB2 loss upon senescence entry disrupts genomic organization and induces CTCF clustering across cell types

• Verfasst von: Zirkel, Anne [VerfasserIn]
• Verfasst von: Mallm, Jan-Philipp [VerfasserIn]
• Verfasst von: Rippe, Karsten [VerfasserIn]
• Titel: HMGB2 loss upon senescence entry disrupts genomic organization and induces CTCF clustering across cell types
• Verf.angabe: Anne Zirkel, Milos Nikolic, Konstantinos Sofiadis, Jan-Philipp Mallm, Chris A. Brackley, Henrike Gothe, Oliver Drechsel, Christian Becker, Janine Altmüller, Natasa Josipovic, Theodore Georgomanolis, Lilija Brant, Julia Franzen, Mirjam Koker, Eduardo G. Gusmao, Ivan G. Costa, Roland T. Ullrich, Wolfgang Wagner, Vassilis Roukos, Peter Nürnberg, Davide Marenduzzo, Karsten Rippe, and Argyris Papantonis
• E-Jahr: 2018
• Jahr: April 26, 2018
• Umfang: 21 S.
• Fussnoten: Gesehen am 23.06.2020
• Titel Quelle: Enthalten in: Molecular cell
• Ort Quelle: [Cambridge, Mass.] : Cell Press, 1997
• Jahr Quelle: 2018
• Band/Heft Quelle: 70(2018), 4, Seite 730-744.e1-e6
• ISSN Quelle: 1097-4164
• DOI: doi:10.1016/j.molcel.2018.03.030
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1694000338

Abstract

Processes like cellular senescence are characterized by complex events giving rise to heterogeneous cell populations. However, the early molecular events driving this cascade remain elusive. We hypothesized that senescence entry is triggered by an early disruption of the cells' three-dimensional (3D) genome organization. To test this, we combined Hi-C, single-cell and population transcriptomics, imaging, and <i>in silico</i> modeling of three distinct cells types entering senescence. Genes involved in DNA conformation maintenance are suppressed upon senescence entry across all cell types. We show that nuclear depletion of the abundant HMGB2 protein occurs early on the path to senescence and coincides with the dramatic spatial clustering of CT<i>CF.</i> Knocking down <i>HMGB2</i> suffices for senescence-induced CTCF clustering and for loop reshuffling, while ectopically expressing <i>HMGB2</i> rescues these effects. Our data suggest that HMGB2-mediated genomic reorganization constitutes a primer for the ensuing senescent program.</p>