REGULATION OF THE E-BETA GENE IN-VIVO - LESSONS FROM E(BETA)(D) TRANSGENIC MICE

We have examined the expression and regulation of the MHC class II E(b eta)(d) gene in both cell lines and in transgenic mice. In transient t ransfection assays, as little as 192 bp of the E(beta)(d) proximal pro moter was sufficient to direct constitutive expression of a reporter g ene in a B cell line and to confer inducibility by IFN-gamma in a macr ophage cell line. To determine if the same E(beta)(d) promoter sequenc es were also sufficient to direct correct expression in vivo, E(beta)( d) transgenes bearing either 4.1 or 0.2 kb of upstream sequence were i ntroduced into an inbred mouse strain with a nonexpressed endogenous E (beta) gene. Expression of both transgenes mirrored the expression of the endogenous I-A protein in thymus, B cells and macrophages with reg ard to both constitutive and cytokine-inducible expression. These resu lts indicate that for the E(beta) gene only 200 bp of proximal promote r sequence are required to achieve tissue-specific and cytokine-induci ble expression. This is in striking contrast to the E(alpha) gene, the only other murine class II gene whose promoter has been analyzed in v ivo, which has been shown to require 2.0 kb of upstream sequence for a ppropriate expression. These data demonstrate, therefore, that the loc ation of critical regulatory elements for the E(beta) and E(alpha) gen es may differ.