Transcriptional targets shared by estrogen receptor-related receptors (ERRs) and estrogen receptor (ER) alpha, but not by ER beta

The physiological activities of estrogens are thought to be mediated by spe cific nuclear receptors, ER alpha and ERP, However, certain tissues, such a s the bone, that are highly responsive to estrogens only express a low leve l of these receptors, Starting from this apparent contradiction, we have ev aluated the potentials of two related receptors ERR alpha and ERR beta to i ntervene in estrogen signaling. ER alpha ERR alpha and ERR beta bind to and activate transcription through both the classical estrogen response elemen t (ERE) and the SF-1 response element (SFRE), In contrast, ER beta DNA-bind ing and transcriptional activity is restricted to the ERE, Accordingly, the osteopontin gene promoter is stimulated through SFRE sequences, by ERRa as well as by ERa, but not by ERP. Analysis of the cross-talk within the ER/E RR subgroup of nuclear receptors thus revealed common targets but also func tional differences between the two ERs.