The X box in promoters of class II major histocompatibility complex genes plays a crucial role in the B-cell-specific and gamma interferon-inducible expression of these genes. The sequence TTCC is located in the pyrimidine tract which extends 5' to and partially overlaps the X box of the DRA promoter. This sequence resembles the core binding site for the Ets family of DNA-binding proteins. In this study, we demonstrate that mutations within the pyrimidine tract which change the TTCC motif, but do not affect the binding of regulatory factor X to the X box, decrease the activity of the DRA promoter in B cells. Furthermore, using electrophoretic mobility shift assays and cotransfection experiments, we demonstrate that Ets-1, but not Ets-2 or PU.1, functionally interacts with the pyrimidine tract and activates the DRA promoter.
Regulatory factor-X binding to mutant HLA-DRA promoter sequences