The glucocorticoid receptor precludes the binding of a transcriptional repressor protein to the long terminal repeat of the mouse mammary tumor virus.
The long terminal repeat (LTR) of the mouse mammary tumor virus was used as a template to examine the dual binding parameters of the glucocorticoid-receptor (GR) and a repressor protein termed Inhibitory Factor 1 (IF1). The receptor binds specifically to the glucocorticoid response element and precludes the binding of IF1 to its juxtaposed binding site within the LTR. When the two DNA targets are separated by the insertion of an additional 52 base pairs, coincident binding of both proteins is observed. Gel retention assays reveal three distinct nucleoprotein complexes. The first complex consists of the receptor and the LTR, the second is comprised of IF1 and DNA and the third is a multiprotein-DNA complex consisting of the GR, IF1 and DNA, migrating at a higher molecular weight position. The inhibition of IF1 binding by the presence of prebound GR leads to the repression of transcription of juxtaposed genes. The GR may act to block access of a sequence, used by the cell to titrate repressor proteins and facilitate the onset of gene expression.
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Department of Pharmacology, Jefferson Cancer Institute, Thomas Jefferson University, Philadelphia, PA 19107.
Kmiec
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D000818:Animals; D001483:Base Sequence; D004278:DNA, Superhelical / Q000378:metabolism; D004279:DNA, Viral / Q000378:metabolism; D015870:Gene Expression; D005814:Genes, Viral; D008324:Mammary Tumor Virus, Mouse / Q000235:genetics*; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D011485:Protein Binding; D012343:RNA, Transfer / Q000235:genetics; D011965:Receptors, Glucocorticoid / Q000502:physiology*; D012091:Repetitive Sequences, Nucleic Acid; D012097:Repressor Proteins / Q000378:metabolism*; D013698:Templates, Genetic; D014158:Transcription, Genetic; D014982:Xenopus laevis
D004278:DNA, Superhelical; D004279:DNA, Viral; D009838:Oligodeoxyribonucleotides; D011965:Receptors, Glucocorticoid; D012097:Repressor Proteins; D012343:RNA, Transfer