Functional Interactions between Retinoic Acid Receptor-related Orphan Nuclear Receptor (ROR) and the Retinoic Acid Receptors in the Regulation of the F-Crystallin Promoter

doi:10.1074/jbc.270.34.20156

Functional Interactions between Retinoic Acid Receptor-related Orphan Nuclear Receptor (ROR) and the Retinoic Acid Receptors in the Regulation of the F-Crystallin Promoter (*)

From the Molecular Oncology Group, Royal Victoria Hospital, Departments of Biochemistry, Medicine and Oncology, McGill University, Montréal, Québec, H3A 1A1, Canada

^¶To whom correspondence should be addressed:
Molecular Oncology Group, Royal Victoria Hospital, 687 Pine Avenue West, Montréal, Québec, H3A 1A1, Canada.
Tel.: 514-843-1479; Fax: 514-843-1478; vgiguere{at}dir.molonc.mcgill.ca

↵^§ Present address: IGBMC, U184 de l'INSERM de Biologie Moléculaire et Génie Génétique, BP163, 67404, Illkirch, Cedex, France.

Abstract

We have previously demonstrated that an everted repeat of the hexamer PuGGTCA located within the F-crystallin promoter mediates activation of the murine F-crystallin gene by retinoic acid and thyroid hormone receptors. Here, we show that the recently identified retinoic acid receptor-related orphan nuclear receptor (RORα) is expressed in the murine lens and activates the F-crystallin promoter. In contrast to the retinoic acid and thyroid hormone receptors, activation of the F-crystallin promoter by RORα requires binding to the single 3′ half-site and spacer sequences of F-crystallin hormone response element (F-HRE). We further demonstrate that RORα-dependent activation is repressed by the competitive binding of retinoic acid receptor/retinoid X receptor heterodimers to the F-HRE in the absence of all-trans-retinoic acid. These studies suggest that the interplay of retinoid receptors and RORα on the F-HRE may constitute an important mechanism regulating F-crystallin gene expression in the murine lens.

Footnotes

↵* This work was supported by Medical Research Council of Canada Grant MT10561 and National Cancer Institute of Canada Grant 3430 (to V. G.), and by a National Science and Engineering Research Council of Canada Post-doctoral Fellowship (to R. A. F.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore by hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
↵¹ The abbreviations used are:

RA

retinoic acid

RAR

retinoic acid receptor

RXR

retinoid X receptor

RORα

retinoic acid receptor-related orphan nuclear receptor

F-HRE

F-crystallin hormone response element

T₃

triiodothyronine

T₃R

T₃ receptor

PCR

polymerase chain reaction

RSV

Rous sarcoma virus

βgal

β-galactosidase

EMSA

electrophoretic mobility shift assay

CAT

chloramphenicol acetyltransferase

bp

base pair(s)

LUC

luciferase

TK

thymidine kinase

RARE

retinoic acid response element

CRBP

cellular retinol binding protein I.
↵²M. Tini, I. Dussault, and V. Giguère, unpublished data.
↵³M. Tini, unpublished observations.
- Received March 10, 1995.