PT  - JOURNAL ARTICLE
AU  - Wang, Shuai
AU  - Lin, Yanke
AU  - Li, Feng
AU  - Qin, Zifei
AU  - Zhou, Ziyue
AU  - Gao, Lu
AU  - Yang, Zemin
AU  - Wang, Zhigang
AU  - Wu, Baojian
TI  - An NF-κB–driven lncRNA orchestrates colitis and circadian clock
AID  - 10.1126/sciadv.abb5202
DP  - 2020 Oct 01
TA  - Science Advances
PG  - eabb5202
VI  - 6
IP  - 42
4099  - http://advances.sciencemag.org/content/6/42/eabb5202.short
4100  - http://advances.sciencemag.org/content/6/42/eabb5202.full
SO  - Sci Adv2020 Oct 01; 6
AB  - 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.