Nucleotide Sequences Required for the Regulation of a Rat α_2u-Globulin Gene by Glucocorticoids

Abstract

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.

Kinetics of mRNA expression of alkaline phosphatase isoenzymes in hepatic tissues from glucocorticoid-treated dogs

“…For example, it has been observed with other genes that a delayed response in expression can be attributabed to the need of a mediator protein that facilitates induction of a secondary gene. [35][36][37][38][39][40][41] Such a mediator protein must reach a critical concentration before transcription exceeds baseline amounts hence the delayed response. It is possible that delayed expression of the CIALP gene following glucocorticoid treatment in dogs is the result of the need to induce expression of an unknown protein (or proteins) to facilitate CIALP transcription.…”