The X box in promoters of class II major histocompatibility complex ge
nes plays a crucial role in the B-cell-specific and gamma interferon-i
nducible expression of these genes. The sequence TTCC is located in th
e pyrimidine tract which extends 5' to and partially overlaps the X bo
x of the DRA promoter. This sequence resembles the core binding site f
or the Ets family of DNA-binding proteins. In this study, we demonstra
te that mutations within the pyrimidine tract which change the TTCC mo
tif, 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, u
sing electrophoretic mobility shift assays and cotransfection experime
nts, we demonstrate that Ets-1, but not Ets-2 or PU.1, functionally in
teracts with the pyrimidine tract and activates the DRA promoter.