A choice between transcriptional enhancement and repression by the v-erbA oncoprotein governed by one nucleotide in a thyroid hormone responsive halfsite

The v-erbA oncoprotein (P75(gag-v-erbA)) can repress thyroid hormone recept or induced transcriptional activation of target genes. A central question i s hom hormone responsive elements in a target gene determine the transcript ional regulation mediated by P75(gag-v-erbA). We addressed this with recept ors chimeric between P75(gag-v-erbA) and thyroid hormone receptor (TR) by t esting their regulatory activities on thyroid hormone response elements (TR Es) differing in the sequence of the consensus core recognition motif AGGTC A. We report here that enhances, TR dependent transcriptional activation is conferred by P75(gag-v-erbA) when the thymidine in the half site recogniti on motif is exchanged for an adenosine. The enhancement mas independent of the DNA binding region of P75(gag-v-erbA), whereas increased expression of corepressor abolished the enhancing effect, The data indicate that the enha ncement results from an impaired DNA binding by the oncoprotein combined wi th an effective scavenging of corepressors. Our data thus suggest the P75(g ag-v-erbA) indirectly can contribute to enhancement of thyroid hormone indu ced gene expression.