TPR is required for cytoplasmic chromatin fragment formation during senescence
- University of Edinburgh, United Kingdom
- Institute of Biomedicine and Biotechnology of Cantabria, Spain
- Université de Montpellier, France
Abstract
During oncogene-induced senescence there are striking changes in the organisation of heterochromatin in the nucleus. This is accompanied by activation of a pro-inflammatory gene expression programme - the senescence associated secretory phenotype (SASP) - driven by transcription factors such as NF-κB. The relationship between heterochromatin re-organisation and the SASP has been unclear. Here we show that TPR, a protein of the nuclear pore complex basket required for heterochromatin re-organisation during senescence, is also required for the very early activation of NF-κB signalling during the stress-response phase of oncogene-induced senescence. This is prior to activation of the SASP and occurs without affecting NF-κB nuclear import. We show that TPR is required for the activation of innate immune signalling at these early stages of senescence and we link this to the formation of heterochromatin-enriched cytoplasmic chromatin fragments thought to bleb off from the nuclear periphery. We show that HMGA1 is also required for cytoplasmic chromatin fragment formation. Together these data suggest that re-organisation of heterochromatin is involved in altered structural integrity of the nuclear periphery during senescence, and that this can lead to activation of cytoplasmic nucleic acid sensing, NF-κB signalling, and activation of the SASP.
Data availability
The RNA-seq and ATAC-seq data generated in this study have been deposited in NCBI GEO, but the data are currently private. Access tokens for reviewers to access these submission data are:RNA seqhttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE264387Access token: qzihsgiwhlqvzopATAC seqhttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE264390Access token: irstugcgzfqrlib
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TPR is required for cytoplasmic chromatin fragment formation during senescenceNCBI Gene Expression Omnibus, GSE264387.
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TPR is required for cytoplasmic chromatin fragment formation during senescenceNCBI Gene Expression Omnibus, GSE264390.
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H3K27ac ChIP-seqNCBI Gene Expression Omnibus, GSE103590.
Article and author information
Author details
Bethany M Bartlett
Tamoghna Chowdhury
Charlene Boumendil
Juan Carlos Acosta
Funding
Medical Research Council (MC_UU_00007/2)
- Wendy A Bickmore
Medical Research Council (MC_UU_00035/7)
- Wendy A Bickmore
Wellcome Trust (217120/Z/19/Z)
- Yatendra Kumar
- Wendy A Bickmore
Cancer Research UK (C47559/A16243)
- Juan Carlos Acosta
Ministry of Science and Innovation, Government of Spain (Proyecto PID2020-117860GB-I00)
- Juan Carlos Acosta
Agence Nationale de la Recherche (ANR-21-CE12-0039)
- Charlene Boumendil
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2024, Bartlett et al.
This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.
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TPR is required for cytoplasmic chromatin fragment formation during senescence
eLife 13:e101702.
https://doi.org/10.7554/eLife.101702
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