Estrogen-related receptor beta interacts with Oct4 to positively regulate Nanog gene expression

Debbie van den Berg, WS Zhang, A Yates, E Engelen, K Takacs, Karel Bezstarosti, Jeroen Demmers, I Chambers, Raymond Poot

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136 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.
Original languageUndefined/Unknown
Pages (from-to)5986-5995
Number of pages10
JournalMolecular and Cellular Biology
Volume28
Issue number19
DOIs
Publication statusPublished - 2008

Research programs

  • EMC MGC-02-21-01

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