Estrogen-Related Receptor Beta Interacts with Oct4 to Positively Regulate Nanog Gene Expression

Adam Yates, Debbie L.C. Van Den Berg, Wensheng Zhang, Erik Engelen, Katalin Takacs, Karel Bezstarosti, Jeroen Demmers, Ian Chambers, Raymond A. Poor

Research output: Contribution to journalArticle

115 Citations (Scopus)

Abstract

Embryonic stem (ES) cell self-renewal is regulated by transcription factors, including Oct4, Sox2, and Nanog. A number of additional transcriptional regulators of ES cell self-renewal have recently been identified, including the orphan nuclear receptor estrogen-related receptor beta (Esrrb). However, the mode of action of Esrrb in ES cells is unknown. Here, using an Oct4 affinity screen, we identify Esrrb as an Oct4 partner protein. Esrrb can interact with Oct4 independently of DNA. Esrrb is recruited near the Oct-Sox element in the Nanog proximal promoter, where it positively regulates Nanog expression. Esrrb recruitment to the Nanog promoter requires both the presence of Oct4 and a degenerate estrogen-related receptor DNA element. Consistent with its role in Nanog regulation, expression of the Esrrb protein within the Oct4-positive ES cell population is mosaic and correlates with the mosaic expression of the Nanog protein. Together with previous reports that Nanog may regulate Esrrb gene expression, our results suggest that Esrrb and Nanog act as part of a feedback regulatory circuit that modulates the fluctuating self-renewal capacity of ES cell populations.

LanguageEnglish
Pages5986-5995
Number of pages10
JournalMolecular and Cellular Biology
Volume28
Issue number19
DOIs
Publication statusPublished - Oct 2008
Externally publishedYes

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Estrogen Receptor beta
Gene Expression
Embryonic Stem Cells
Orphan Nuclear Receptors
DNA
Estrogen Receptors
Population
Proteins
Transcription Factors

Cite this

Yates, A., Van Den Berg, D. L. C., Zhang, W., Engelen, E., Takacs, K., Bezstarosti, K., ... Poor, R. A. (2008). Estrogen-Related Receptor Beta Interacts with Oct4 to Positively Regulate Nanog Gene Expression. Molecular and Cellular Biology, 28(19), 5986-5995. https://doi.org/10.1128/MCB.00301-08
Yates, Adam ; Van Den Berg, Debbie L.C. ; Zhang, Wensheng ; Engelen, Erik ; Takacs, Katalin ; Bezstarosti, Karel ; Demmers, Jeroen ; Chambers, Ian ; Poor, Raymond A. / Estrogen-Related Receptor Beta Interacts with Oct4 to Positively Regulate Nanog Gene Expression. In: Molecular and Cellular Biology. 2008 ; Vol. 28, No. 19. pp. 5986-5995.
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Yates, A, Van Den Berg, DLC, Zhang, W, Engelen, E, Takacs, K, Bezstarosti, K, Demmers, J, Chambers, I & Poor, RA 2008, 'Estrogen-Related Receptor Beta Interacts with Oct4 to Positively Regulate Nanog Gene Expression', Molecular and Cellular Biology, vol. 28, no. 19, pp. 5986-5995. https://doi.org/10.1128/MCB.00301-08

Estrogen-Related Receptor Beta Interacts with Oct4 to Positively Regulate Nanog Gene Expression. / Yates, Adam; Van Den Berg, Debbie L.C.; Zhang, Wensheng; Engelen, Erik; Takacs, Katalin; Bezstarosti, Karel; Demmers, Jeroen; Chambers, Ian; Poor, Raymond A.

In: Molecular and Cellular Biology, Vol. 28, No. 19, 10.2008, p. 5986-5995.

Research output: Contribution to journalArticle

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Yates A, Van Den Berg DLC, Zhang W, Engelen E, Takacs K, Bezstarosti K et al. Estrogen-Related Receptor Beta Interacts with Oct4 to Positively Regulate Nanog Gene Expression. Molecular and Cellular Biology. 2008 Oct;28(19):5986-5995. https://doi.org/10.1128/MCB.00301-08