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Title 

Transcriptional cross talk between orphan nuclear receptor ERRgamma and transmembrane transcription factor ATF6alpha coordinates endoplasmic reticulum stress response

Authors 

J MisraD K KimW ChoiS H KooChul Ho LeeS H BackR J KaufmanH S Choi

Publisher 

Oxford University Press

Issue Date 

2013

Citation 

Nucleic Acids Research, vol. 41, no. 14, pp. 6960-6974

Abstract 

Orphan nuclear receptor ERRγ is a member of nuclear receptor superfamily that regulates several important cellular processes including hepatic glucose and alcohol metabolism. However, mechanistic understanding of transcriptional regulation of the ERRγ gene remains to be elucidated. Here, we report that activating transcription factor 6α (ATF6α), an endoplasmic reticulum (ER)-membrane-bound basic leucine zipper (bZip) transcription factor, directly regulates ERRγ gene expression in response to ER stress. ATF6α binds to ATF6α responsive element in the ERRγ promoter. The transcriptional coactivator peroxisome proliferator-activated receptor gamma coactivator 1-α (PGC-1α) is required for this transactivation. Chromatin immunoprecipitation (ChIP) assay confirmed the binding of both ATF6α and PGC1α on the ERRγ promoter. ChIP assay demonstrated histone H3 and H4 acetylation occurs at the ATF6α and PGC1α binding site. Of interest, ERRγ along with PGC1α induce ATF6α gene transcription upon ER stress. ERRγ binds to an ERRγ responsive element in the ATF6α promoter. ChIP assay confirmed that both ERRγ and PGC1α bind to a site in the ATF6α promoter that exhibits histone H3 and H4 acetylation. Overall, for the first time our data show a novel pathway of cross talk between nuclear receptors and ER-membrane-bound transcription factors and suggest a positive feed-forward loop regulates ERRγ and ATF6α gene transcription.

ISSN 

0305-1048

Link 

http://dx.doi.org/10.1093/nar/gkt429

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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