ROR alpha augments thyroid hormone receptor-mediated transcriptional activation.

Published

Journal Article

This study is designed to clarify the role of an orphan nuclear hormone receptor, ROR alpha, 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 ROR alpha1 was performed. When ROR alpha1 and TR were cotransfected into CV1 cells, ROR alpha1 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 ROR alpha bound to all TREs tested as a monomer, no (or weak) TR and ROR alpha1 heterodimer formation was observed on various TREs except when a putative ROR-response element was present. The transactivation by ROR alpha1 on a ROR-response element, which does not contain a TRE, was not enhanced by TR. The effect of ROR alpha1 on the TREs is unique, because, whereas other nuclear hormone receptors (such as vitamin D receptor) may competitively bind to TRE to exert dominant negative function, ROR alpha1 augmented TR action. These results indicate that ROR alpha1 may modify the effect of liganded TR on TH-responsive genes. Because TR and ROR alpha are coexpressed in cerebellar Purkinje cells, and perinatal hypothyroid animals and ROR alpha-disrupted animals show similar abnormalities of this cell type, cross-talk between these two receptors may play a critical role in Purkinje cell differentiation.

Full Text

Duke Authors

Cited Authors

  • Koibuchi, N; Liu, Y; Fukuda, H; Takeshita, A; Yen, PM; Chin, WW

Published Date

  • March 1999

Published In

Volume / Issue

  • 140 / 3

Start / End Page

  • 1356 - 1364

PubMed ID

  • 10067863

Pubmed Central ID

  • 10067863

International Standard Serial Number (ISSN)

  • 0013-7227

Digital Object Identifier (DOI)

  • 10.1210/endo.140.3.6562

Language

  • eng

Conference Location

  • United States