RT Journal Article
SR Electronic
T1 An NF-κB–driven lncRNA orchestrates colitis and circadian clock
JF Science Advances
JO Sci Adv
FD American Association for the Advancement of Science
SP eabb5202
DO 10.1126/sciadv.abb5202
VO 6
IS 42
A1 Wang, Shuai
A1 Lin, Yanke
A1 Li, Feng
A1 Qin, Zifei
A1 Zhou, Ziyue
A1 Gao, Lu
A1 Yang, Zemin
A1 Wang, Zhigang
A1 Wu, Baojian
YR 2020
UL http://advances.sciencemag.org/content/6/42/eabb5202.abstract
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.