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Molecular cloning and characterization of a factor that binds the human glucocorticoid receptor gene and represses its expression.

LeClerc S., Palaniswami R., Xie B.X., Govindan M.V.

The human DNA binding factor GRF-1, which associates with the promoter region of the glucocorticoid receptor gene (hGR gene), is a repressor of glucocorticoid receptor transcription. The GRF-1 cDNA was cloned using polyclonal antibodies against the purified protein. The deduced amino acid sequence from the cDNA sequences show the presence of three sequence motifs characteristic of a zinc finger and one motif suggestive of a leucine zipper in which 1 cysteine is found instead of all leucines. The GRF-1 expressed in COS-1 cells has a molecular weight of 95,000 and enhances the homologous down-regulation of wild-type hGR gene expression. Biochemical analysis suggests that GRF-1 interaction is sequence specific and that transcriptional efficacy of GRF-1 is regulated through its interaction with specific sequence motif, namely 5'-GAAGGAGGTAGCGAGAAAAGAAACTG-GAGAAACTCGGT.GG-3'. The GRF-1 mRNA is 6.5 kilobases long in rat liver and human MCF-7 cells, and its level is regulated by glucocorticoids.

J. Biol. Chem. 266:17333-17340(1991) [PubMed] [Europe PMC]

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