Regulation of pluripotency in mouse embryonic stem cells by Esrrb-mediated Nanog expression

Abstract

Estrogen-related receptor beta (Esrrb), an orphan nuclear receptor, belongs to the NR3B subgroup of nuclear receptor superfamily. Esrrb recognizes the estrogen-related receptor response element (ERRE) through its DNA-binding domain and constitutively activates the target genes without natural ligands. In addition to master transcription factors such as Oct4, Sox2 and Nanog, Esrrb has been also implicated in maintenance of pluripotency in mouse embryonic stem cells (mESCs), however, detailed molecular mechanism of action of Esrrb in this process has not been detailed. Here, we demonstrate that Esrrb regulates Nanog expression through binding to ERRE located proximal to the Nanog promoter. We further found that Ncoa3 and Prmt1 function as transcriptional coactivators through direct interactions with Esrrb for Nanog expression. In addition to identifying Esrrb as a novel DNA-binding transcription factor for Nanog expression, we provide a molecular mechanism for the coactivator function of Ncoa3 and Prmt1 in maintenance of pluripotency in mESCs.