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HMGB1 coordinates SASP‐related chromatin folding and RNA homeostasis on the path to senescence
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....
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8224457/ https://www.ncbi.nlm.nih.gov/pubmed/34166567 http://dx.doi.org/10.15252/msb.20209760 |
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author | Sofiadis, Konstantinos Josipovic, Natasa Nikolic, Milos Kargapolova, Yulia Übelmesser, Nadine Varamogianni‐Mamatsi, Vassiliki Zirkel, Anne Papadionysiou, Ioanna Loughran, Gary Keane, James Michel, Audrey Gusmao, Eduardo G Becker, Christian Altmüller, Janine Georgomanolis, Theodore Mizi, Athanasia Papantonis, Argyris |
author_facet | Sofiadis, Konstantinos Josipovic, Natasa Nikolic, Milos Kargapolova, Yulia Übelmesser, Nadine Varamogianni‐Mamatsi, Vassiliki Zirkel, Anne Papadionysiou, Ioanna Loughran, Gary Keane, James Michel, Audrey Gusmao, Eduardo G Becker, Christian Altmüller, Janine Georgomanolis, Theodore Mizi, Athanasia Papantonis, Argyris |
author_sort | Sofiadis, Konstantinos |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8224457 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-82244572021-07-06 HMGB1 coordinates SASP‐related chromatin folding and RNA homeostasis on the path to senescence Sofiadis, Konstantinos Josipovic, Natasa Nikolic, Milos Kargapolova, Yulia Übelmesser, Nadine Varamogianni‐Mamatsi, Vassiliki Zirkel, Anne Papadionysiou, Ioanna Loughran, Gary Keane, James Michel, Audrey Gusmao, Eduardo G Becker, Christian Altmüller, Janine Georgomanolis, Theodore Mizi, Athanasia Papantonis, Argyris Mol Syst Biol Articles 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. John Wiley and Sons Inc. 2021-06-24 /pmc/articles/PMC8224457/ /pubmed/34166567 http://dx.doi.org/10.15252/msb.20209760 Text en © 2021 The Authors. Published under the terms of the CC BY 4.0 license https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Articles Sofiadis, Konstantinos Josipovic, Natasa Nikolic, Milos Kargapolova, Yulia Übelmesser, Nadine Varamogianni‐Mamatsi, Vassiliki Zirkel, Anne Papadionysiou, Ioanna Loughran, Gary Keane, James Michel, Audrey Gusmao, Eduardo G Becker, Christian Altmüller, Janine Georgomanolis, Theodore Mizi, Athanasia Papantonis, Argyris HMGB1 coordinates SASP‐related chromatin folding and RNA homeostasis on the path to senescence |
title | HMGB1 coordinates SASP‐related chromatin folding and RNA homeostasis on the path to senescence |
title_full | HMGB1 coordinates SASP‐related chromatin folding and RNA homeostasis on the path to senescence |
title_fullStr | HMGB1 coordinates SASP‐related chromatin folding and RNA homeostasis on the path to senescence |
title_full_unstemmed | HMGB1 coordinates SASP‐related chromatin folding and RNA homeostasis on the path to senescence |
title_short | HMGB1 coordinates SASP‐related chromatin folding and RNA homeostasis on the path to senescence |
title_sort | hmgb1 coordinates sasp‐related chromatin folding and rna homeostasis on the path to senescence |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8224457/ https://www.ncbi.nlm.nih.gov/pubmed/34166567 http://dx.doi.org/10.15252/msb.20209760 |
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