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BMAL1 moonlighting as a gatekeeper for LINE1 repression and cellular senescence in primates
Aging in humans is intricately linked with alterations in circadian rhythms concomitant with physiological decline and stem cell exhaustion. However, whether the circadian machinery directly regulates stem cell aging, especially in primates, remains poorly understood. In this study, we found that de...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8989534/ https://www.ncbi.nlm.nih.gov/pubmed/35286396 http://dx.doi.org/10.1093/nar/gkac146 |
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author | Liang, Chuqian Ke, Qiong Liu, Zunpeng Ren, Jie Zhang, Weiqi Hu, Jianli Wang, Zehua Chen, Hong Xia, Kai Lai, Xingqiang Wang, Qiaoran Yang, Kuan Li, Wei Wu, Zeming Wang, Chao Yan, Haoteng Jiang, Xiaoyu Ji, Zhejun Ma, Miyang Long, Xiao Wang, Si Wang, Huating Sun, Hao Belmonte, Juan Carlos Izpisua Qu, Jing Xiang, Andy Peng Liu, Guang-Hui |
author_facet | Liang, Chuqian Ke, Qiong Liu, Zunpeng Ren, Jie Zhang, Weiqi Hu, Jianli Wang, Zehua Chen, Hong Xia, Kai Lai, Xingqiang Wang, Qiaoran Yang, Kuan Li, Wei Wu, Zeming Wang, Chao Yan, Haoteng Jiang, Xiaoyu Ji, Zhejun Ma, Miyang Long, Xiao Wang, Si Wang, Huating Sun, Hao Belmonte, Juan Carlos Izpisua Qu, Jing Xiang, Andy Peng Liu, Guang-Hui |
author_sort | Liang, Chuqian |
collection | PubMed |
description | Aging in humans is intricately linked with alterations in circadian rhythms concomitant with physiological decline and stem cell exhaustion. However, whether the circadian machinery directly regulates stem cell aging, especially in primates, remains poorly understood. In this study, we found that deficiency of BMAL1, the only non-redundant circadian clock component, results in an accelerated aging phenotype in both human and cynomolgus monkey mesenchymal progenitor cells (MPCs). Unexpectedly, this phenotype was mainly attributed to a transcription-independent role of BMAL1 in stabilizing heterochromatin and thus preventing activation of the LINE1-cGAS-STING pathway. In senescent primate MPCs, we observed decreased capacity of BMAL1 to bind to LINE1 and synergistic activation of LINE1 expression. Likewise, in the skin and muscle tissues from the BMAL1-deficient cynomolgus monkey, we observed destabilized heterochromatin and aberrant LINE1 transcription. Altogether, these findings uncovered a noncanonical role of BMAL1 in stabilizing heterochromatin to inactivate LINE1 that drives aging in primate cells. |
format | Online Article Text |
id | pubmed-8989534 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-89895342022-04-08 BMAL1 moonlighting as a gatekeeper for LINE1 repression and cellular senescence in primates Liang, Chuqian Ke, Qiong Liu, Zunpeng Ren, Jie Zhang, Weiqi Hu, Jianli Wang, Zehua Chen, Hong Xia, Kai Lai, Xingqiang Wang, Qiaoran Yang, Kuan Li, Wei Wu, Zeming Wang, Chao Yan, Haoteng Jiang, Xiaoyu Ji, Zhejun Ma, Miyang Long, Xiao Wang, Si Wang, Huating Sun, Hao Belmonte, Juan Carlos Izpisua Qu, Jing Xiang, Andy Peng Liu, Guang-Hui Nucleic Acids Res Gene regulation, Chromatin and Epigenetics Aging in humans is intricately linked with alterations in circadian rhythms concomitant with physiological decline and stem cell exhaustion. However, whether the circadian machinery directly regulates stem cell aging, especially in primates, remains poorly understood. In this study, we found that deficiency of BMAL1, the only non-redundant circadian clock component, results in an accelerated aging phenotype in both human and cynomolgus monkey mesenchymal progenitor cells (MPCs). Unexpectedly, this phenotype was mainly attributed to a transcription-independent role of BMAL1 in stabilizing heterochromatin and thus preventing activation of the LINE1-cGAS-STING pathway. In senescent primate MPCs, we observed decreased capacity of BMAL1 to bind to LINE1 and synergistic activation of LINE1 expression. Likewise, in the skin and muscle tissues from the BMAL1-deficient cynomolgus monkey, we observed destabilized heterochromatin and aberrant LINE1 transcription. Altogether, these findings uncovered a noncanonical role of BMAL1 in stabilizing heterochromatin to inactivate LINE1 that drives aging in primate cells. Oxford University Press 2022-03-14 /pmc/articles/PMC8989534/ /pubmed/35286396 http://dx.doi.org/10.1093/nar/gkac146 Text en © The Author(s) 2022. Published by Oxford University Press on behalf of Nucleic Acids Research. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Gene regulation, Chromatin and Epigenetics Liang, Chuqian Ke, Qiong Liu, Zunpeng Ren, Jie Zhang, Weiqi Hu, Jianli Wang, Zehua Chen, Hong Xia, Kai Lai, Xingqiang Wang, Qiaoran Yang, Kuan Li, Wei Wu, Zeming Wang, Chao Yan, Haoteng Jiang, Xiaoyu Ji, Zhejun Ma, Miyang Long, Xiao Wang, Si Wang, Huating Sun, Hao Belmonte, Juan Carlos Izpisua Qu, Jing Xiang, Andy Peng Liu, Guang-Hui BMAL1 moonlighting as a gatekeeper for LINE1 repression and cellular senescence in primates |
title | BMAL1 moonlighting as a gatekeeper for LINE1 repression and cellular senescence in primates |
title_full | BMAL1 moonlighting as a gatekeeper for LINE1 repression and cellular senescence in primates |
title_fullStr | BMAL1 moonlighting as a gatekeeper for LINE1 repression and cellular senescence in primates |
title_full_unstemmed | BMAL1 moonlighting as a gatekeeper for LINE1 repression and cellular senescence in primates |
title_short | BMAL1 moonlighting as a gatekeeper for LINE1 repression and cellular senescence in primates |
title_sort | bmal1 moonlighting as a gatekeeper for line1 repression and cellular senescence in primates |
topic | Gene regulation, Chromatin and Epigenetics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8989534/ https://www.ncbi.nlm.nih.gov/pubmed/35286396 http://dx.doi.org/10.1093/nar/gkac146 |
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