Transcriptional cross talk between orphan nuclear receptor ERRγ and transmembrane transcription factor ATF6α coordinates endoplasmic reticulum stress response

Jagannath Misra, Don Kyu Kim, Woogyun Choi, Seung-Hoi Koo, Chul Ho Lee, Sung Hoon Back, Randal J. Kaufman, Hueng Sik Choi

Research output: Contribution to journalArticle

16 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)6960-6974
Number of pages15
JournalNucleic Acids Research
Volume41
Issue number14
DOIs
Publication statusPublished - 2013 Aug 1

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Activating Transcription Factor 6
Orphan Nuclear Receptors
Endoplasmic Reticulum Stress
Transcription factors
Transcription Factors
Histones
Chromatin Immunoprecipitation
Chromatin
Acetylation
Assays
Genes
Transcription
Cytoplasmic and Nuclear Receptors
Endoplasmic Reticulum
Basic-Leucine Zipper Transcription Factors
Membranes
Metabolism
Gene expression
Transcriptional Activation

ASJC Scopus subject areas

  • Genetics

Cite this

Transcriptional cross talk between orphan nuclear receptor ERRγ and transmembrane transcription factor ATF6α coordinates endoplasmic reticulum stress response. / Misra, Jagannath; Kim, Don Kyu; Choi, Woogyun; Koo, Seung-Hoi; Lee, Chul Ho; Back, Sung Hoon; Kaufman, Randal J.; Choi, Hueng Sik.

In: Nucleic Acids Research, Vol. 41, No. 14, 01.08.2013, p. 6960-6974.

Research output: Contribution to journalArticle

Misra, Jagannath ; Kim, Don Kyu ; Choi, Woogyun ; Koo, Seung-Hoi ; Lee, Chul Ho ; Back, Sung Hoon ; Kaufman, Randal J. ; Choi, Hueng Sik. / Transcriptional cross talk between orphan nuclear receptor ERRγ and transmembrane transcription factor ATF6α coordinates endoplasmic reticulum stress response. In: Nucleic Acids Research. 2013 ; Vol. 41, No. 14. pp. 6960-6974.
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