Retinoid X receptor isoforms a and p differentially regulate 3,5,3′‐triiodothyronine‐induced transcription

Various heterodimers of the thyroid hormone receptor (TR) with other nuclear hormone receptors confer a wide range of transcriptional activities on thyroid hormone response elements (TREs) in the presence of the thyroid hormone (T3). The present study analyzed the potential roles of retinoid X receptor (RXR) isoforms α and β in T3‐mediated transcription on a well characterized TRE, a direct repeat of AGGTCA separated by four nucleo‐tides (DR4), using electrophoretic mobility shift assays and transient transfection in CV‐1 cells. We demonstrated that RXRa supressed liganded TRα‐induced transcription while RXRβ did not although both TRα/RXRα and TRα/RXRβ heterodimers were the predominant forms bound to the TRE‐DR4 in the presence of T3. We further demonstrated using Scatchard analysis that the two heterodimers had similar affinities for the TRE‐DR4. All these observations suggest that the TRE‐DR4 accomodates different types of TR/RXR heterodimers for a more finely tuned transcriptional response to T3