title: Steroid-responsive sequences in the human glucocorticoid receptor gene 1A promoter.
abstract: At least three promoters (1A, 1B, and 1C) control the expression of mRNA transcripts for the human glucocorticoid receptor (hGR) protein. An hGR 1A promoter/exon sequence (-218/+269) contains at least 12 deoxyribonuclease (DNase) I footprints that contain bound protein. Whereas four of these footprints (FP6, FP7, FP8, and FP11) contain bound hGR in protein-DNA complexes that are formed, only two (FP7 and FP11) appear to be important for the up-regulation of hGR 1A promoter/exon activity in T-lymphoblasts. Furthermore, the activity of these DNA elements depends upon the promoter context, leading to a redundant and complex regulation of expression of the hGR 1A promoter/exon. FP7 appears to be required for hormonal responsiveness in the absence of upstream sequences (+41/+191), whereas the hormonal responsiveness of FP11 requires a functional, adjacent FP12 DNA sequence. FP12 contains overlapping binding sites for the protooncogene transcription factors c-Myb and c-Ets. It seems likely that binding of either c-Myb or c-Ets to FP12 is necessary for the direct or indirect binding of the hGR to FP11 (a nonconsensus glucocorticoid response element), and the resultant steroid-responsiveness of the hGR 1A promoter/exon sequence. We propose that the identity of the accessory transcription factor bound to FP12 (c-Myb or c-Ets) may determine the nature of regulation (positive or negative) of hGR gene expression by hormone, and that this may be important for hormone-induced apoptosis in T cell acute lymphoblastic leukemia.
authors.affiliation: Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, 533 Bolivar Street, New Orleans, LA 70112, USA.
authors.forename: Chuan-Dong
authors.initials: CD
authors.lastname: Geng
authors.forename: Wayne V
authors.initials: WV
authors.lastname: Vedeckis
mesh_terms: D001665:Binding Sites; D004247:DNA / Q000378:metabolism; D018983:DNA Footprinting; D003850:Deoxyribonuclease I / Q000378:metabolism; D003907:Dexamethasone / Q000378:metabolism*; D005091:Exons / Q000502:physiology; D006801:Humans; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D050783:Proto-Oncogene Proteins c-ets; D020598:Proto-Oncogene Proteins c-myb / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000096:biosynthesis / Q000235:genetics*; D017422:Sequence Analysis, DNA; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D020598:Proto-Oncogene Proteins c-myb; D011965:Receptors, Glucocorticoid; D014157:Transcription Factors; D003907:Dexamethasone; D004247:DNA; D003850:Deoxyribonuclease I