Cross-talk among ROR alpha 1 and the Rev-erb family of orphan nuclear receptors.
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.
Salk Institute for Biological Studies, Gene Expression Laboratory, San Diego, California 92186-5800.
B M
BM
Forman
J
J
Chen
B
B
Blumberg
S A
SA
Kliewer
R
R
Henshaw
E S
ES
Ong
R M
RM
Evans
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D004247:DNA / Q000378:metabolism*; D018076:DNA, Complementary / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D008099:Liver / Q000737:chemistry; D051379:Mice; D008969:Molecular Sequence Data; D005810:Multigene Family; D057094:Nuclear Receptor Subfamily 1, Group F, Member 1; D020794:Receptor Protein-Tyrosine Kinases; D057050:Receptor Tyrosine Kinase-like Orphan Receptors; D011956:Receptors, Cell Surface / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism*; D011988:Receptors, Thyroid Hormone; D012045:Regulatory Sequences, Nucleic Acid; D015534:Trans-Activators; D014158:Transcription, Genetic
D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D057094:Nuclear Receptor Subfamily 1, Group F, Member 1; D011956:Receptors, Cell Surface; D018160:Receptors, Cytoplasmic and Nuclear; D011988:Receptors, Thyroid Hormone; D015534:Trans-Activators; D004247:DNA; C078716:ROR1 protein, human; D020794:Receptor Protein-Tyrosine Kinases; D057050:Receptor Tyrosine Kinase-like Orphan Receptors