Molecular Endocrinology, Vol 8, 1253-1261, Copyright © 1994 by Endocrine Society

ARTICLES

Cross-talk among ROR alpha 1 and the Rev-erb family of orphan nuclear receptors

BM Forman, J Chen, B Blumberg, SA Kliewer, R Henshaw, ES Ong and RM Evans
Salk Institute for Biological Studies, Gene Expression Laboratory, San Diego, California 92186-5800.

We have cloned Rev-erb beta, a novel isoform of the Rev-erb alpha orphan nuclear receptor. The DNA binding domains of Rev-erb alpha and beta are highly related to each other and to the retinoic acid related orphan receptor (ROR)/RZR subfamily of nuclear receptors. Indeed, we find that all three receptors bind as monomers to the sequence AATGT- AGGTCA. Whereas ROR alpha 1 constitutively activates transcription through this sequence, both isoforms of Rev-erb are inactive. When coexpressed, both Rev-erb isoforms suppress the transcriptional activity of ROR alpha 1. Our data define Rev-erb and ROR/RZR as a family of related receptors with opposing activities on overlapping regulatory networks.

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