Purified glucocorticoid receptors bind selectively in vitro to a cloned DNA fragment that mediates a delayed secondary response to glucocorticoids in vivo.
We have identified and characterized a 206-base-pair region downstream from rat alpha 2u-globulin promoter that specifically mediates a delayed secondary response to glucocorticoids. Unlike positive primary glucocorticoid response elements (GREs), this regulatory element, termed delayed sGRE, dictates an inductive process preceded by a time lag of several hours and blocked by the protein synthesis inhibitor cycloheximide. Reminiscent of GREs and negative GREs (nGREs), a delayed sGRE confers hormonal regulation upon a linked heterologous promoter from a downstream position with respect to transcription start site and, remarkably, also interacts selectively with purified glucocorticoid receptor. These results imply that receptor binding to a delayed sGRE in vivo may mediate certain secondary responses to glucocorticoid hormones.
E. A. Doisy Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, MO 63104.
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Hess
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Meenakshi
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Chan
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Carlstedt-Duke
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Gustafsson
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Payvar
D000510:Alpha-Globulins / Q000235:genetics*; D000818:Animals; D001667:Binding, Competitive; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics* / Q000378:metabolism; D004268:DNA-Binding Proteins; D003907:Dexamethasone / Q000494:pharmacology*; D005796:Genes; D007700:Kinetics; D007739:L Cells / Q000378:metabolism; D051379:Mice; D009710:Nucleotide Mapping; D011401:Promoter Regions, Genetic; D051381:Rats; D011965:Receptors, Glucocorticoid / Q000187:drug effects / Q000302:isolation & purification / Q000378:metabolism*; D015183:Restriction Mapping; D014158:Transcription, Genetic; D014162:Transfection
D000510:Alpha-Globulins; D004268:DNA-Binding Proteins; D011965:Receptors, Glucocorticoid; C013803:alpha 2u globulin; D003907:Dexamethasone; D004247:DNA; D015500:Chloramphenicol O-Acetyltransferase