Parry, AJ;
Hoare, M;
Bihary, D;
Hansel-Hertsch, R;
Smith, S;
Tomimatsu, K;
Mannion, E;
... Narita, M; + view all
(2018)
NOTCH-mediated non-cell autonomous regulation of chromatin structure during senescence.
Nature Communications
, 9
(1840)
10.1038/s41467-018-04283-9.
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Abstract
Senescent cells interact with the surrounding microenvironment achieving diverse functional outcomes. We have recently identified that NOTCH1 can drive ‘lateral induction’ of a unique senescence phenotype in adjacent cells by specifically upregulating the NOTCH ligand JAG1. Here we show that NOTCH signalling can modulate chromatin structure autonomously and non-autonomously. In addition to senescence-associated heterochromatic foci (SAHF), oncogenic RAS-induced senescent (RIS) cells exhibit a massive increase in chromatin accessibility. NOTCH signalling suppresses SAHF and increased chromatin accessibility in this context. Strikingly, NOTCH-induced senescent cells, or cancer cells with high JAG1 expression, drive similar chromatin architectural changes in adjacent cells through cell–cell contact. Mechanistically, we show that NOTCH signalling represses the chromatin architectural protein HMGA1, an association found in multiple human cancers. Thus, HMGA1 is involved not only in SAHFs but also in RIS-driven chromatin accessibility. In conclusion, this study identifies that the JAG1–NOTCH–HMGA1 axis mediates the juxtacrine regulation of chromatin architecture.
| Type: | Article |
|---|---|
| Title: | NOTCH-mediated non-cell autonomous regulation of chromatin structure during senescence |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1038/s41467-018-04283-9 |
| Publisher version: | https://doi.org/10.1038/s41467-018-04283-9 |
| Language: | English |
| Additional information: | This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
| Keywords: | Science & Technology, Multidisciplinary Sciences, Science & Technology - Other Topics, GENE-EXPRESSION DATA, GROUP-A PROTEINS, HISTONE ACETYLATION, NUCLEOSOMAL DNA, HETEROCHROMATIN FORMATION, STROMAL SENESCENCE, SIGNALING PATHWAY, HMGI-C, CANCER, MOBILITY |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10049298 |
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