An NF-kB–driven lncRNA orchestrates colitis and circadian clock
research target：NF-kB,colitis,circadian clock
Periodicals：Sci Adv
IF：13.118
Cooperative Unit:Jinan University College of Pharmacy
Time of publication：October，2020
Summary
We uncover a cycling and NF-kB–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-kB activation in experimental colitis transcriptionally drives Lnc-UC through direct binding to two kB 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-kB/Nlrp3 repressor) to inactivate NF-kB signaling and Nlrp3 inflam- masome 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.
