Complex regulation of Ly-6E gene transcription in T cells by IFNs

The complexity of IFN-mediated regulation of the murine Ly-6E gene in T cel l lines is highlighted by the following observations: 1) multiple regulator y regions are present within different parts of the Ly-6E promoter and are necessary for IFN inducibility of the Ly-6E gene, 2) multiple transcription factors including Oct-1 and Oct-2 and the high mobility group (HMG) protei n HMGI(Y) bind to regulatory elements present within the G region required far bath IFN-alpha beta and IFN-gamma responses, 3) mutational analysis of the G region reveals that a complex interaction exists between the factors binding to this region as shown by their mutual interdependence for detecti on in DMSA, and 4) inhibition of expression of HMG proteins by antisense HM GI-C RNA in EL4 cells causes the loss of IFN-alpha beta and IFN-gamma induc ibility of the endogenous Ly-6 gene. These findings taken together suggest that, in response to IFN treatment, an HMG protein-dependent complex involv ing multiple regulatory factors is assembled and is required for IFN induci bility of the Ly-6E gene.