Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Animals
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Base Sequence
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Binding Sites
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DNA / metabolism*
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DNA, Complementary / genetics
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism*
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Liver / chemistry
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Mice
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Molecular Sequence Data
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Multigene Family
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Nuclear Receptor Subfamily 1, Group F, Member 1
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Receptor Protein-Tyrosine Kinases
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Receptor Tyrosine Kinase-like Orphan Receptors
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Receptors, Cell Surface / metabolism*
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Receptors, Cytoplasmic and Nuclear / genetics
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Receptors, Cytoplasmic and Nuclear / metabolism*
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Receptors, Thyroid Hormone*
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Regulatory Sequences, Nucleic Acid
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Trans-Activators
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Transcription, Genetic*
Substances
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DNA, Complementary
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DNA-Binding Proteins
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Nuclear Receptor Subfamily 1, Group F, Member 1
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Receptors, Cell Surface
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Receptors, Cytoplasmic and Nuclear
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Receptors, Thyroid Hormone
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Trans-Activators
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DNA
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ROR1 protein, human
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Receptor Protein-Tyrosine Kinases
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Receptor Tyrosine Kinase-like Orphan Receptors