Transcriptional activities of the orphan nuclear receptor ERR alpha (estrogen receptor-related receptor-alpha)

Estrogen receptor-related receptor alpha (ERR alpha) is an orphan nuclear r eceptor closely related to the estrogen receptor (ER), whose expression cov ers various stages of embryonic development and persists in certain adult t issues. We show that ERR alpha binds as a homodimer on a specific target se quence, the SFRE (SF-1 response element), already known to respond to the o rphan nuclear receptor SF-1. Target sequences that are related to the SFRE and that discriminate between ERR alpha and SF-1 were identified. We have a lso analyzed the transcriptional properties of the ERR alpha originating fr om various species. All ERR alpha orthologs act as potent transactivators t hrough the consensus SFRE. ERR alpha activity depends on the putative AF2AD domain, as well as on a serum compound that is withdrawn by charcoal treat ment, suggesting the existence of a critical regulating factor brought by s erum.