Nucleotide sequences required for the regulation of a rat alpha 2u-globulin gene by glucocorticoids.
alpha 2u-Globulin is a rat protein of as yet unknown function whose synthesis can be induced by glucocorticoids and several other hormones. Induction by glucocorticoids is a secondary response to the hormone: protein synthesis is required before the hormone can exert its stimulatory effect on alpha 2u-globulin transcription. We have used the linker-scanning mutagenesis procedure, followed by transfer of the mutant genes into mouse L-cells for analysis of their phenotype, to determine sequences within a cloned alpha 2u-globulin promoter that are required for its regulation by glucocorticoids. Mutations between positions -115 and -160 abolish or greatly reduce the inducibility of alpha 2u-globulin by the hormone. Mutations just upstream from this region, between positions -177 and -220, have an opposite effect; they increase induction two- to fourfold.
D000510:Alpha-Globulins / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D003513:Cycloheximide / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D004640:Emetine / Q000494:pharmacology; D004720:Endonucleases / Q000378:metabolism; D005786:Gene Expression Regulation; D005938:Glucocorticoids / Q000494:pharmacology*; D007700:Kinetics; D009154:Mutation; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D015719:Single-Strand Specific DNA and RNA Endonucleases; D014162:Transfection
D000510:Alpha-Globulins; D005938:Glucocorticoids; D012333:RNA, Messenger; D003907:Dexamethasone; D003513:Cycloheximide; D004720:Endonucleases; D015719:Single-Strand Specific DNA and RNA Endonucleases; D004640:Emetine