Zirkel, Anne, Nikolic, Milos ORCID: 0000-0003-0029-7601, Sofiadis, Konstantinos, Mallm, Jan-Philipp, Brackley, Chris A., Gothe, Henrike, Drechsel, Oliver, Becker, Christian, Altmueller, Janine, Josipovic, Natasa, Georgomanolis, Theodore, Brant, Lilija, Franzen, Julia, Koker, Mirjam, Gusmao, Eduardo G., Costa, Ivan G. ORCID: 0000-0003-2890-8697, Ullrich, Roland T., Wagner, Wolfgang ORCID: 0000-0002-1971-3217, Roukos, Vassilis ORCID: 0000-0002-5065-3937, Nuernberg, Peter, Marenduzzo, Davide ORCID: 0000-0003-3974-4915, Rippe, Karsten ORCID: 0000-0001-9951-9395 and Papantonis, Argyris ORCID: 0000-0001-7551-1073 (2018). HMGB2 Loss upon Senescence Entry Disrupts Genomic Organization and Induces CTCF Clustering across Cell Types. Mol. Cell, 70 (4). S. 730 - 751. CAMBRIDGE: CELL PRESS. ISSN 1097-4164

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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 in silico 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 CTCF. Knocking down HMGB2 suffices for senescence-induced CTCF clustering and for loop reshuffling, while ectopically expressing HMGB2 rescues these effects. Our data suggest that HMGB2-mediated genomic reorganization constitutes a primer for the ensuing senescent program.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Zirkel, AnneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nikolic, MilosUNSPECIFIEDorcid.org/0000-0003-0029-7601UNSPECIFIED
Sofiadis, KonstantinosUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mallm, Jan-PhilippUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brackley, Chris A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gothe, HenrikeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Drechsel, OliverUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Becker, ChristianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Altmueller, JanineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Josipovic, NatasaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Georgomanolis, TheodoreUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brant, LilijaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Franzen, JuliaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Koker, MirjamUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gusmao, Eduardo G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Costa, Ivan G.UNSPECIFIEDorcid.org/0000-0003-2890-8697UNSPECIFIED
Ullrich, Roland T.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wagner, WolfgangUNSPECIFIEDorcid.org/0000-0002-1971-3217UNSPECIFIED
Roukos, VassilisUNSPECIFIEDorcid.org/0000-0002-5065-3937UNSPECIFIED
Nuernberg, PeterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Marenduzzo, DavideUNSPECIFIEDorcid.org/0000-0003-3974-4915UNSPECIFIED
Rippe, KarstenUNSPECIFIEDorcid.org/0000-0001-9951-9395UNSPECIFIED
Papantonis, ArgyrisUNSPECIFIEDorcid.org/0000-0001-7551-1073UNSPECIFIED
URN: urn:nbn:de:hbz:38-186370
DOI: 10.1016/j.molcel.2018.03.030
Journal or Publication Title: Mol. Cell
Volume: 70
Number: 4
Page Range: S. 730 - 751
Date: 2018
Publisher: CELL PRESS
Place of Publication: CAMBRIDGE
ISSN: 1097-4164
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
CHROMATIN LANDSCAPE; TOPOLOGICAL DOMAINS; PROTEIN HMGB2; HI-C; TRANSCRIPTION; DNA; HETEROCHROMATIN; BINDING; CANCER; IDENTIFICATIONMultiple languages
Biochemistry & Molecular Biology; Cell BiologyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/18637

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