| First Author | Wang S | Year | 2020 |
| Journal | Sci Adv | Volume | 6 |
| Issue | 42 | PubMed ID | 33055157 |
| Mgi Jnum | J:340220 | Mgi Id | MGI:6798438 |
| Doi | 10.1126/sciadv.abb5202 | Citation | Wang S, et al. (2020) An NF-kappaB-driven lncRNA orchestrates colitis and circadian clock. Sci Adv 6(42) |
| abstractText | We uncover a cycling and NF-kappaB-driven lncRNA (named Lnc-UC) that epigenetically modifies transcription of circadian clock gene Rev-erbalpha, 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-kappaB activation in experimental colitis transcriptionally drives Lnc-UC through direct binding to two kappaB sites. Lnc-UC ablation disrupts colonic expressions of clock genes in mice; particularly, Rev-erbalpha is down-regulated and its diurnal rhythm is blunted. Consistently, Lnc-UC promotes expression of Rev-erbalpha (a known dual NF-kappaB/Nlrp3 repressor) to inactivate NF-kappaB 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-erbalpha transcription and expression. In addition, we identify a human Lnc-UC that has potential to promote Rev-erbalpha expression and restrain inflammations. |
