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An NF-?B-driven lncRNA orchestrates colitis and circadian clock.


ABSTRACT: We uncover a cycling and NF-?B-driven lncRNA (named Lnc-UC) that epigenetically modifies transcription of circadian clock gene Rev-erb?, 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-?B activation in experimental colitis transcriptionally drives Lnc-UC through direct binding to two ?B sites. Lnc-UC ablation disrupts colonic expressions of clock genes in mice; particularly, Rev-erb? is down-regulated and its diurnal rhythm is blunted. Consistently, Lnc-UC promotes expression of Rev-erb? (a known dual NF-?B/Nlrp3 repressor) to inactivate NF-?B 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-erb? transcription and expression. In addition, we identify a human Lnc-UC that has potential to promote Rev-erb? expression and restrain inflammations.

SUBMITTER: Wang S 

PROVIDER: S-EPMC7556837 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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An NF-κB-driven lncRNA orchestrates colitis and circadian clock.

Wang Shuai S   Lin Yanke Y   Li Feng F   Qin Zifei Z   Zhou Ziyue Z   Gao Lu L   Yang Zemin Z   Wang Zhigang Z   Wu Baojian B  

Science advances 20201014 42


We uncover a cycling and NF-κB-driven lncRNA (named <i>Lnc-UC</i>) that epigenetically modifies transcription of circadian clock gene <i>Rev-erb</i>α, thereby linking circadian clock to colitis. Cycling expression of <i>Lnc-UC</i> is generated by the central clock protein Bmal1 via an E-box element. NF-κB activation in experimental colitis transcriptionally drives <i>Lnc-UC</i> through direct binding to two κB sites. <i>Lnc-UC</i> ablation disrupts colonic expressions of clock genes in mice; par  ...[more]

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