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

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...

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Bibliographic Details
Published in:The FASEB journal 2021-04, Vol.35 (4), p.e21507-n/a
Main Authors: Kwon, Paul Kwangho, Kim, Hyo‐Min, Kang, Byunghee, Kim, Sung Wook, Hwang, Sung‐Min, Im, Sin‐Hyeog, Roh, Tae‐Young, Kim, Kyong‐Tai
Format: Article
Language:English
Subjects:
circadian rhythm
hnRNP K
poly(C) motif
RORγ
transcription
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Summary: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.
ISSN:0892-6638
1530-6860
DOI:10.1096/fj.202002076R