Sofiadis et al. 2021 (PRJNA720951)

General Details

Title HMGB1 coordinates SASP-related chromatin folding and RNA homeostasis on the path to senescence [Ribo-seq]
Organism
Number of Samples 6
Release Date 2021/04/09 00:00
Sequencing Types
Protocol Details

Study Links

Repository Details

SRA SRP314256
ENA SRP314256
GEO GSE171780
BioProject PRJNA720951

Publication

Title
Authors Sofiadis K,Josipovic N,Nikolic M,Kargapolova Y,Übelmesser N,Varamogianni-Mamatsi V,Zirkel A,Papadionysiou I,Loughran G,Keane J,Michel A,Gusmao EG,Becker C,Altmüller J,Georgomanolis T,Mizi A,Papantonis A
Journal Molecular systems biology
Publication Date 2021 Jun
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. © 2021 The Authors. Published under the terms of the CC BY 4.0 license.
PMC PMC8224457
PMID 34166567
DOI
Run Accession Study Accession Scientific Name Cell Line Library Type Treatment GWIPS-viz Trips-Viz Reads BAM BigWig (F) BigWig (R)
SRR14200571 PRJNA720951 Homo sapiens IMR90 Ribo-Seq
SRR14200572 PRJNA720951 Homo sapiens IMR90 Ribo-Seq
SRR14200573 PRJNA720951 Homo sapiens IMR90 Ribo-Seq
SRR14200574 PRJNA720951 Homo sapiens IMR90 Ribo-Seq
SRR14200575 PRJNA720951 Homo sapiens IMR90 Ribo-Seq
SRR14200576 PRJNA720951 Homo sapiens IMR90 Ribo-Seq
Run Accession Study Accession Scientific Name Cell Line Library Type Treatment GWIPS-viz Trips-Viz Reads BAM BigWig (F) BigWig (R)

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