Transcriptional Activities of the Orphan Nuclear Receptor ERR (Estrogen Receptor-Related Receptor- )

Estrogen receptor-related receptor � (ERR�) isan orphan nuclear receptor closely related to the estrogen receptor (ER), whose expression covers various stages of embryonic development and persists in certain adult tissues. We show that ERR� binds as a homodimer on a specific target sequence, the SFRE (SF-1 response element), already known to respond to the orphan nuclear receptor SF-1. Target sequences that are related to the SFRE and that discriminate between ERR � and SF-1 were identified. We have also analyzed the transcriptional properties of the ERR � originating from various species. All ERR � orthologs act as potent transactivators through the consensus SFRE. ERR � activity depends on the putative AF2AD domain, as well as on a serum compound that is withdrawn by charcoal treatment, suggesting the existence of a critical regulating factor brought by serum. (Molecular Endocrinology 13: 764–773, 1999)