Role of the N terminus in DNA recognition by the v-erb A protein, an oncogenic derivative of a thyroid hormone receptor.

The v-erb A oncogene is a mutated derivative of a normal cellular locus (c-erb A alpha) encoding a thyroid hormone receptor. Although both the v-erb A protein and thyroid hormone receptor bind to DNA, the DNA sequence specificity of the viral oncoprotein is altered from that of the normal cellular receptor. Intriguingly, amino acid differences in both the zinc-finger domain and in a less-characterized N-terminal region of the v- and c-erb A polypeptides are jointly responsible for these differences in DNA specificity. We demonstrate here that this newly recognized N-terminal determinant of DNA specificity appears to function by restricting the DNA sequence repertoire manifested by the zinc-finger domain itself. The unique presence of a tyrosine in the N terminus of the thyroid hormone receptor acts to abrogate this restriction, thereby permitting this receptor to utilize response elements containing nonconsensus half-sites. The ability of the N terminus to modulate the DNA recognition properties of nuclear hormone receptors extends to the retinoic acid receptor and contributes to the distinct DNA specificities displayed by the retinoic acid and thyroid hormone receptors.