The neuron-specific RC3/neurogranin gene is regulated by thyroid hormone at the transcriptional level in brain and in cultured neuronal cells. Regulation in vivo displays exquisite regional selectivity which is not due to differential distribution of thyroid receptors and is most probably related to region-specific trans-acting elements. We have previously identified an intronic thyroid hormone responsive element in the human RC3 gene homolog, NRGN. In a search for cis-acting elements that might contribute to the specificity of thyroid regulation, we have identified a novel sequence, TTCCAAAATGG, which binds to a developmentally regulated protein, and interferes with T3 transactivation.