Universität zu Köln

Sofiadis, Konstantinos, Josipovic, Natasa ORCID: 0000-0001-7683-0869, Nikolic, Milos ORCID: 0000-0003-0029-7601, Kargapolova, Yulia ORCID: 0000-0001-7541-5778, Ubelmesser, Nadine, Varamogianni-Mamatsi, Vassiliki, Zirkel, Anne, Papadionysiou, Ioanna, Loughran, Gary, Keane, James ORCID: 0000-0001-7640-8326, Michel, Audrey, Gusmao, Eduardo G., Becker, Christian, Altmueller, Janine, Georgomanolis, Theodore, Mizi, Athanasia and Papantonis, Argyris (2021). HMGB1 coordinates SASP-related chromatin folding and RNA homeostasis on the path to senescence. Mol. Syst. Biol., 17 (6). HOBOKEN: WILEY. ISSN 1744-4292

Full text not available from this repository.

Abstract

Spatial organization and gene expression of mammalian chromosomes are maintained and regulated in conjunction with cell cycle progression. This is perturbed once cells enter senescence and the highly abundant HMGB1 protein is depleted from nuclei to act as an extracellular proinflammatory stimulus. Despite its physiological importance, we know little about the positioning of HMGB1 on chromatin and its nuclear roles. To address this, we mapped HMGB1 binding genome-wide in two primary cell lines. We integrated ChIP-seq and Hi-C with graph theory to uncover clustering of HMGB1-marked topological domains that harbor genes involved in paracrine senescence. Using simplified Cross-Linking and Immuno-Precipitation and functional tests, we show that HMGB1 is also a bona fide RNA-binding protein (RBP) binding hundreds of mRNAs. It presents an interactome rich in RBPs implicated in senescence regulation. The mRNAs of many of these RBPs are directly bound by HMGB1 and regulate availability of SASP-relevant transcripts. Our findings reveal a broader than hitherto assumed role for HMGB1 in coordinating chromatin folding and RNA homeostasis as part of a regulatory loop controlling cell-autonomous and paracrine senescence.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Sofiadis, Konstantinos UNSPECIFIED UNSPECIFIED UNSPECIFIED Josipovic, Natasa UNSPECIFIED orcid.org/0000-0001-7683-0869 UNSPECIFIED Nikolic, Milos UNSPECIFIED orcid.org/0000-0003-0029-7601 UNSPECIFIED Kargapolova, Yulia UNSPECIFIED orcid.org/0000-0001-7541-5778 UNSPECIFIED Ubelmesser, Nadine UNSPECIFIED UNSPECIFIED UNSPECIFIED Varamogianni-Mamatsi, Vassiliki UNSPECIFIED UNSPECIFIED UNSPECIFIED Zirkel, Anne UNSPECIFIED UNSPECIFIED UNSPECIFIED Papadionysiou, Ioanna UNSPECIFIED UNSPECIFIED UNSPECIFIED Loughran, Gary UNSPECIFIED UNSPECIFIED UNSPECIFIED Keane, James UNSPECIFIED orcid.org/0000-0001-7640-8326 UNSPECIFIED Michel, Audrey UNSPECIFIED UNSPECIFIED UNSPECIFIED Gusmao, Eduardo G. UNSPECIFIED UNSPECIFIED UNSPECIFIED Becker, Christian UNSPECIFIED UNSPECIFIED UNSPECIFIED Altmueller, Janine UNSPECIFIED UNSPECIFIED UNSPECIFIED Georgomanolis, Theodore UNSPECIFIED UNSPECIFIED UNSPECIFIED Mizi, Athanasia UNSPECIFIED UNSPECIFIED UNSPECIFIED Papantonis, Argyris UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-583389
DOI:	10.15252/msb.20209760
Journal or Publication Title:	Mol. Syst. Biol.
Volume:	17
Number:	6
Date:	2021
Publisher:	WILEY
Place of Publication:	HOBOKEN
ISSN:	1744-4292
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language DNA DAMAGE; PROTEIN HMGB1; SEQ DATA; BINDING; GENOME; IDENTIFICATION; DOMAINS; PROGRAM; P53; RECRUITMENT Multiple languages Biochemistry & Molecular Biology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/58338