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

The v-erbA oncoprotein (P75gag-v-erbA) can repress thyroid hormone receptor induced transcriptional activation of target genes. A central question is how hormone responsive elements in a target gene determine the transcriptional regulation mediated by P75gag-v-erbA. We addressed this with receptors chimeric between P75gag-v-erbA and thyroid hormone receptor (TR) by testing their regulatory activities on thyroid hormone response elements (TREs) differing in the sequence of the consensus core recognition motif AGGTCA. We report here that enhances, TR dependent transcriptional activation is conferred by P75gag-v-erbA when the thymidine in the half site recognition motif is exchanged for an adenosine. The enhancement was independent of the DNA binding region of P75gag-v-erbA, whereas increased expression of corepressor abolished the enhancing effect. The data indicate that the enhancement results from an impaired DNA binding by the oncoprotein combined with an effective scavenging of corepressors. Our data thus suggest the P75gag-v-erbA indirectly can contribute to enhancement of thyroid hormone induced gene expression.