Document 0821
 DOCN  M9470821
 TI    Rat Rev-erbA alpha, an orphan receptor related to thyroid hormone
       receptor, binds to specific thyroid hormone response elements.
 DT    9409
 AU    Spanjaard RA; Nguyen VP; Chin WW; Department of Medicine, Brigham and
       Women's Hospital, Boston, MA; 02115.
 SO    Mol Endocrinol. 1994 Mar;8(3):286-95. Unique Identifier : AIDSLINE
       MED/94285930
 AB    Rat Rev-erbA alpha (rRev), which is related to thyroid hormone receptor
       (TR), is a conserved member of the nuclear hormone receptor superfamily
       whose physiological roles are unknown (orphan receptor). We studied DNA
       binding of rRev in vitro by electrophoretic mobility shift assay. A
       fusion protein was constructed, called NGR.Rev, containing part of the N
       terminus of the glucocorticoid receptor fused to nearly full-length
       rRev. Inasmuch as rRev and TR share homology in their DNA-binding
       domains, we tested binding to three different thyroid hormone response
       elements (TREs) in which the half-sites are arranged in different
       orientations. NGR.Rev bound direct repeats (DR4), but not palindromic
       (TREpal) or inverted palindromic (F2H) repeats. Also, transfection of
       CV1 cells with a reporter gene containing the luciferase gene under
       control of the inducible thymidine kinase promoter resulted in an
       increase in luciferase activity when NGR.Rev was cotransfected and when
       the thymidine kinase promoter contained DR4. In addition, a series of
       deletions in the ligand-binding domain of NGR.Rev revealed regions that
       can modulate DNA binding. Finally, we studied DNA binding of bacterially
       produced fusion proteins that contain the DNA-binding domains of rRev or
       rTR alpha fused to glutathione S-transferase, to a panel of natural
       TREs. Our results indicate that Rev binds DNA with a different
       specificity than TR alpha-1 and might be involved in the regulation of a
       subset of thyroid hormone-regulated genes.
 DE    Amino Acid Sequence  Animal  Base Sequence  Cell Line  Cloning,
       Molecular  Dose-Response Relationship, Drug
       DNA/ANALYSIS/GENETICS/METABOLISM  DNA-Binding
       Proteins/GENETICS/*METABOLISM  Genes, env/*GENETICS  Glutathione
       Transferases/GENETICS  Ligands  Molecular Sequence Data  Mutation
       Promoter Regions (Genetics)  Protein Binding
       Proteins/GENETICS/*METABOLISM  Rats  Receptors, Thyroid
       Hormone/GENETICS/*METABOLISM  Sequence Homology, Amino Acid  Sequence
       Homology, Nucleic Acid  Transcription, Genetic  Transfection  Zinc
       Fingers  JOURNAL ARTICLE

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       protected by Copyright Law (Title 17, U.S.Code).