EXPRESSION OF A NOVEL MEMBER OF ESTROGEN RESPONSE ELEMENT-BINDING NUCLEAR RECEPTORS IS RESTRICTED TO THE EARLY STAGES OF CHORION FORMATION DURING MOUSE EMBRYOGENESIS

Members of the nuclear hormone receptor gene family of transcription f actors have been shown to be expressed in characteristic patterns duri ng mouse organogenesis and postnatal development. Using an RT-PCR base d screening assay, we have identified nuclear receptors expressed in e mbryonal carcinoma stem cells. One of the cDNAs characterized, mERR-2, was found to be expressed exclusively during a narrow developmental w indow in trophoblast progenitor cells between days 6.5 and 7.5 post co itum (p.c.). From 8.5 days p.c. and onwards, the mERR-2 gene activity evaded detection as analysed by in situ hybridization. We also show th at the mERR-2 gene product and the estrogen receptor share a common ta rget DNA-sequence recognition specificity unique among members of the gene family. Furthermore, efficient homodimerization and DNA-binding o f the orphan receptor mERR-2 was found to be dependent on interaction with the heat shock protein 90, a molecular chaperone hitherto recogni zed to interact only with the steroid hormone receptor subgroup of nuc lear receptors. Based on our results we suggest that the mouse orphan receptor mERR-2 has the potential to regulate overlapping gene network s with the estrogen receptor and may participate in signal transductio n pathways during a short developmental period coinciding with the for mation of the chorion.