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hnRNP K supports the maintenance of RORγ circadian rhythm through ERK signaling.

Authors :
Kwon PK
Kim HM
Kang B
Kim SW
Hwang SM
Im SH
Roh TY
Kim KT
Source :
FASEB journal : official publication of the Federation of American Societies for Experimental Biology [FASEB J] 2021 Apr; Vol. 35 (4), pp. e21507.
Publication Year :
2021

Abstract

Retinoic acid-related orphan receptor γ (RORγ) maintains the circadian rhythms of its downstream genes. However, the mechanism behind the transcriptional activation of RORγ itself remains unclear. Here, we demonstrate that transcription of RORγ is activated by heterogeneous nuclear ribonucleoprotein K (hnRNP K) via the poly(C) motif within its proximal promoter. Interestingly, we confirmed the binding of endogenous hnRNP K within RORγ1 and RORγ2 promoter along with the recruitment of RNA polymerase 2 through chromatin immunoprecipitation (ChIP). Furthermore, an assay for transposase accessible chromatin (ATAC)-qPCR showed that hnRNP K induced higher chromatin accessibility within the RORγ1 and RORγ2 promoter. Then we found that the knockdown of hnRNP K lowers RORγ mRNA oscillation amplitude in both RORγ and RORγ-dependent metabolic genes. Moreover, we demonstrated that time-dependent extracellular signal-regulated kinase (ERK) activation controls mRNA oscillation of RORγ and RORγ-dependent metabolic genes through hnRNP K. Taken together, our results provide new insight into the regulation of RORγ by hnRNP K as a transcriptional activator, along with its physiological significance in metabolism.<br /> (© 2021 Federation of American Societies for Experimental Biology.)

Details

Language :
English
ISSN :
1530-6860
Volume :
35
Issue :
4
Database :
MEDLINE
Journal :
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
Publication Type :
Academic Journal
Accession number :
33724572
Full Text :
https://doi.org/10.1096/fj.202002076R