Regulation of the E_β gene in vivo: Lessons from E_β^d transgenic mice

We have examined the expression and regulation of the MHC class II E_β^d gene in both cell lines and in transgenic mice. In transient transfection assays, as little as 192 bp of the E_β^d proximal promoter was sufficient to direct constitutive expression of a reporter gene in a B cell line and to confer inducibility by IFN-γ in a macrophage cell line. To determine if the same E_β^d promoter sequences were also sufficient to direct correct expression in vivo, E_β^d transgenes bearing either 4.1 or 0.2 kb of upstream sequence were introduced into an inbred mouse strain with a nonexpressed endogenous E_β gene. Expression of both transgenes mirrored the expression of the endogenous I-A protein in thymus, B cells and macrophages with regard to both constitutive and cytokine-inducible expression. These results indicate that for the E_β gene only 200 bp of proximal promoter sequence are required to achieve tissue-specific and cytokine-inducible expression. This is in striking contrast to the E_α gene, the only other murine class II gene whose promoter has been analyzed in vivo, which has been shown to require 2.0 kb of upstream sequence for appropriate expression. These data demonstrate, therefore, that the location of critical regulatory elements for the E_β and E_α genes may differ.