Leading science, pioneering therapies
CRM Publications

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

TitleEstrogen-related receptor beta interacts with Oct4 to positively regulate Nanog gene expression.
Publication TypeJournal Article
Year of Publication2008
Authorsvan den Berg DLC, Zhang W, Yates A, Engelen E, Takacs K, Bezstarosti K, Demmers J, Chambers I, Poot RA
JournalMol Cell Biol
Date Published2008 Oct
KeywordsAnimals, Cell Line, Embryonic Stem Cells, Homeodomain Proteins, Mice, Octamer Transcription Factor-3, Receptors, Estrogen

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.

Alternate JournalMol. Cell. Biol.
PubMed ID18662995
PubMed Central IDPMC2547019
Grant List / / Biotechnology and Biological Sciences Research Council / United Kingdom
/ / Medical Research Council / United Kingdom
/ / Wellcome Trust / United Kingdom