RT Journal Article
SR Electronic
T1 Dynamic changes of enhancer and super enhancer landscape in degenerated nucleus pulposus cells
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e202201854
DO 10.26508/lsa.202201854
VO 6
IS 6
A1 Li, Guowang
A1 Kang, Yuxiang
A1 Feng, Xiangling
A1 Wang, Guohua
A1 Yuan, Yue
A1 Li, Zhenhua
A1 Du, Lilong
A1 Xu, Baoshan
YR 2023
UL http://www.life-science-alliance.org/content/6/6/e202201854.abstract
AB Inflammatory cascade and extracellular matrix remodeling have been identified as pivotal pathological factors in the progression of intervertebral disc degeneration (IDD), but the mechanisms underlying the aberrant activation of transcription during nucleus pulposus (NP) cell degeneration remain elusive. Super-enhancers (SEs) are large clusters of adjacent lone enhancers, which control expression modes of cellular fate and pathogenic genes. Here, we showed that SEs underwent tremendous remodeling during NP cell degeneration and that SE-related transcripts were most abundant in inflammatory cascade and extracellular matrix remodeling processes. Inhibition of cyclin-dependent kinase 7, a transcriptional kinase–mediated transcriptional initiation in trans-acting SE complex, constricted the transcription of inflammatory cascades, and extracellular matrix remodeling–related genes such as IL1β and MMP3 in NP cells, meanwhile, also restrained the transcription of Mmp16, Tnfrsf21, and Il11ra1 to retard IDD in rats. In summary, our findings clarify SEs control the transcription of genes associated with inflammatory cascade and extracellular matrix remodeling during NP cell degeneration and identify inhibition of the cyclin-dependent kinase 7, required for SE-mediated transcriptional activation, as a therapeutic option for IDD.