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Complex Regulation of Ly-6E Gene Transcription in T Cells by IFNs¹

Mehran M. Khodadoust^*, Khuda Dad Khan and Alfred L. M. Bothwell^2,*

^* Section of Immunobiology, Yale University School of Medicine, New Haven, CT 06520; and Department of Medicine, Divisions of Hematology and Oncology, Duke University Medical Center, Durham, NC 27710

The complexity of IFN-mediated regulation of the murine Ly-6E gene in T cell lines is highlighted by the following observations: 1) multiple regulatory 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) protein HMGI(Y) bind to regulatory elements present within the G region required for both IFN-ß and IFN- 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 detection in DMSA, and 4) inhibition of expression of HMG proteins by antisense HMGI-C RNA in EL4 cells causes the loss of IFN-ß and IFN- inducibility of the endogenous Ly-6 gene. These findings taken together suggest that, in response to IFN treatment, an HMG protein-dependent complex involving multiple regulatory factors is assembled and is required for IFN inducibility of the Ly-6E gene.

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