IDENTIFICATION OF A NUCLEAR-PROTEIN FROM RAT DEVELOPING BRAIN AS HETERODIMERIZATION PARTNER WITH THYROID-HORMONE RECEPTOR-BETA

Thyroid hormone receptors (TR) are ligand-activated transcription fact ors that modulate the expression of certain target genes in a developm ental and tissue-specific manner. These specificities are determined b y the tissue distribution of the TR isoforms al and pi, the structure of the thyroid hormone response element (TRE) bound by the receptor, a nd heterodimerization partners. Among these, retinoid X receptors (RXR ) have been recognized as the principal partners for TR. The present w ork reports the identification of a novel nuclear protein from 19-day- old embryonic rat brain that displays a distinct interaction pattern w ith TR isoforms at the level of the TRE of two genes known to be diffe rentially expressed and regulated by thyroid hormone (T-3): the ubiqui tous malic enzyme and the brain-specific myelin basic protein. Electro phoretic gel mobility shift, assays demonstrate that only TR beta 1 fo rms a specific complex with the rat brain nuclear factor on the myelin basic protein-TRE, but not on the malic enzyme-TRE. Thus, the interac tion is selectively determined by both the receptor isoform and the st ructure of the TRE. The expression of this brain nuclear factor is res tricted to the perinatal period, when myelination is sensitive to T-3. Gel supershift assays with RXR-specific antibodies indicate that this factor is not one of the known RXR isoforms. However, it is most like ly a new member of the RXR subfamily because it could be supershifted with an antibody raised against the highly conserved DNA-binding domai n of RXRs.