RORα Augments Thyroid Hormone Receptor-Mediated Transcriptional Activation1

This study is designed to clarify the role of an orphan nuclear hormone receptor, RORα, on thyroid hormone (TH) receptor (TR)-mediated transcription on a TH-response element (TRE). A transient transfection study using various TREs [i.e., F2 (chick lysozyme TRE), DR4 (direct repeat), and palindrome TRE] and TR and RORα1 was performed. When RORα1 and TR were cotransfected into CV1 cells, RORα1 enhanced the transactivation by liganded-TR on all TREs tested without an effect on basal repression by unliganded TR. By electrophoretic mobility shift assay, on the other hand, although RORα bound to all TREs tested as a monomer, no (or weak) TR and RORα1 heterodimer formation was observed on various TREs except when a putative ROR-response element was present. The transactivation by RORα1 on a ROR-response element, which does not contain a TRE, was not enhanced by TR. The effect of RORα1 on the TREs is unique, because, whereas other nuclear hormone receptors (such as vitamin D receptor) may competitively bind to TR...