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An NF-κB–driven lncRNA orchestrates colitis and circadian clock
We uncover a cycling and NF-κB–driven lncRNA (named Lnc-UC) that epigenetically modifies transcription of circadian clock gene Rev-erbα, thereby linking circadian clock to colitis. Cycling expression of Lnc-UC is generated by the central clock protein Bmal1 via an E-box element. NF-κB activation in...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Association for the Advancement of Science
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7556837/ https://www.ncbi.nlm.nih.gov/pubmed/33055157 http://dx.doi.org/10.1126/sciadv.abb5202 |
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author | Wang, Shuai Lin, Yanke Li, Feng Qin, Zifei Zhou, Ziyue Gao, Lu Yang, Zemin Wang, Zhigang Wu, Baojian |
author_facet | Wang, Shuai Lin, Yanke Li, Feng Qin, Zifei Zhou, Ziyue Gao, Lu Yang, Zemin Wang, Zhigang Wu, Baojian |
author_sort | Wang, Shuai |
collection | PubMed |
description | We uncover a cycling and NF-κB–driven lncRNA (named Lnc-UC) that epigenetically modifies transcription of circadian clock gene Rev-erbα, thereby linking circadian clock to colitis. Cycling expression of Lnc-UC is generated by the central clock protein Bmal1 via an E-box element. NF-κB activation in experimental colitis transcriptionally drives Lnc-UC through direct binding to two κB sites. Lnc-UC ablation disrupts colonic expressions of clock genes in mice; particularly, Rev-erbα is down-regulated and its diurnal rhythm is blunted. Consistently, Lnc-UC promotes expression of Rev-erbα (a known dual NF-κB/Nlrp3 repressor) to inactivate NF-κB signaling and Nlrp3 inflammasome in macrophages. Furthermore, Lnc-UC ablation sensitizes mice to experimental colitis and abolishes the diurnal rhythmicity in disease severity. Mechanistically, Lnc-UC physically interacts with Cbx1 protein to reduce its gene silencing activity via H3K9me3, thereby enhancing Rev-erbα transcription and expression. In addition, we identify a human Lnc-UC that has potential to promote Rev-erbα expression and restrain inflammations. |
format | Online Article Text |
id | pubmed-7556837 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | American Association for the Advancement of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-75568372020-10-26 An NF-κB–driven lncRNA orchestrates colitis and circadian clock Wang, Shuai Lin, Yanke Li, Feng Qin, Zifei Zhou, Ziyue Gao, Lu Yang, Zemin Wang, Zhigang Wu, Baojian Sci Adv Research Articles We uncover a cycling and NF-κB–driven lncRNA (named Lnc-UC) that epigenetically modifies transcription of circadian clock gene Rev-erbα, thereby linking circadian clock to colitis. Cycling expression of Lnc-UC is generated by the central clock protein Bmal1 via an E-box element. NF-κB activation in experimental colitis transcriptionally drives Lnc-UC through direct binding to two κB sites. Lnc-UC ablation disrupts colonic expressions of clock genes in mice; particularly, Rev-erbα is down-regulated and its diurnal rhythm is blunted. Consistently, Lnc-UC promotes expression of Rev-erbα (a known dual NF-κB/Nlrp3 repressor) to inactivate NF-κB signaling and Nlrp3 inflammasome in macrophages. Furthermore, Lnc-UC ablation sensitizes mice to experimental colitis and abolishes the diurnal rhythmicity in disease severity. Mechanistically, Lnc-UC physically interacts with Cbx1 protein to reduce its gene silencing activity via H3K9me3, thereby enhancing Rev-erbα transcription and expression. In addition, we identify a human Lnc-UC that has potential to promote Rev-erbα expression and restrain inflammations. American Association for the Advancement of Science 2020-10-14 /pmc/articles/PMC7556837/ /pubmed/33055157 http://dx.doi.org/10.1126/sciadv.abb5202 Text en Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). https://creativecommons.org/licenses/by-nc/4.0/ 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 use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited. |
spellingShingle | Research Articles Wang, Shuai Lin, Yanke Li, Feng Qin, Zifei Zhou, Ziyue Gao, Lu Yang, Zemin Wang, Zhigang Wu, Baojian An NF-κB–driven lncRNA orchestrates colitis and circadian clock |
title | An NF-κB–driven lncRNA orchestrates colitis and circadian clock |
title_full | An NF-κB–driven lncRNA orchestrates colitis and circadian clock |
title_fullStr | An NF-κB–driven lncRNA orchestrates colitis and circadian clock |
title_full_unstemmed | An NF-κB–driven lncRNA orchestrates colitis and circadian clock |
title_short | An NF-κB–driven lncRNA orchestrates colitis and circadian clock |
title_sort | nf-κb–driven lncrna orchestrates colitis and circadian clock |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7556837/ https://www.ncbi.nlm.nih.gov/pubmed/33055157 http://dx.doi.org/10.1126/sciadv.abb5202 |
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