The X1 box of HLA-G promoter is a target site for RFX and Sp1 factors

HLA-G gene regulation was investigated with regards to homologies among the pathways regulating both classical MHC class I and MHC class II gene expre ssion. They include four conserved cis-acting regulatory elements located i n the proximal promoter region referred to as the W/S/Z box, the X box that is comprised of the X1 and X2 halves, and the Y box with an inverted CCAAT site. The X1 box is the binding site for the ubiquitous RFX complex consis ting of three subunits; the X2 box is bound by the X2BP/ATF/CREB family fac tors. The basic S-X-Y regulatory module interacts with CIITA, which is expr essed constitutively in APCs, but may be inducible in others cell types by IFN-gamma. Within HLA-G gene promoter the only conserved motifs are S and X 1 boxes. We thus investigated the binding capacity of the HLA-G X box in co mparison to that of HLA-DRA and HLA-E. We demonstrate that X2 box mutations in HLA-G promoter affect the binding of ATF/CREB family factors and may pr ivilege the X2 box to access by other shared factors. The X1 box is the tar get for RFX complex and an additional factor we identified as Spl. We propo se that the X region in the HLA-G gene promoter might participate to the co mbination of factors which play a role in HLA-G gene activation. (C) Americ an Society for Histocompatibility and Immunogenetics, 2000. Published by El sevier Science Inc.