C-ERBA, BUT NOT V-ERBA, COMPETES WITH A PUTATIVE ERYTHROID REPRESSOR FOR BINDING TO THE CARBONIC-ANHYDRASE-II PROMOTER

The carbonic anhydrase II (CAII) gene is the only known gene identifie d as direct target for v-ErbA-mediated repression in avian erythroleuk emic cells transformed by Avian Erythroblastosis Virus (AEV). This gen e is transcriptionally activated by thyroid hormone (T3) in normal ery throcytic cells. In this work we have analysed the molecular basis of the transcriptional control of the CAII gene by c-ErbA and v-ErbA. We show that several domains in the promoter control hormonal regulation of transcription. One domain proximal to the TATA box mediates T3 resp onse but contains no identified binding site for c-ErbA. An other doma in termed PAL2 is approximately 600 bp upstream the transcription init iation site and contains a c-ErbA binding site. We show that when it i s associated to a heterologous promoter this site mediates transcripti onal repression in erythrocytic cells but not in HeLa cells. Moreover, this site binds a nuclear erythrocyte-specific factor that we called NFX, which is different from c-ErbA. Heterodimers between c-ErbA and t he 9-cis retinoic acid receptor (RXR) compete with NFX for binding to PAL2. In contrast, v-ErbA alone or in association with RXR is a very p oor competitor and is unable to chase NFX out of the PAL2 site. We pro pose that NFX is a transcription repressor whose activity is inhibited by c-ErbA but not v-ErbA. This mechanism might contribute to the over all regulation of the carbonic anhydrase II promoter. These data illus trate another possible mechanism through which v-ErbA might antagonize the function of c-ErbA in controlling gene expression.