A conserved sequence motif exists at the 5' end of all major histocompatibility complex class II genes. This motif consists of the 14-base X and Y boxes separated by a short stretch of variable sequence. In this report, we provide evidence that the X and Y boxes play an important role in controlling transcription of the murine class II gene El. We have developed transgenic mouse lines that carry Ea genes cleanly deleted for either the X or Y box and have compared the expression of these mutant transgenes with that of a nondeleted control. Both the X and the Y segments appear critical for accurate and efficient transcription of Ek. The most drastic effect is seen with y-interferon-treated macrophages, where deletion of the Y box completely abrogates transcription initiated by the normal promoter. In addition, we identify proteins from nuclear extracts that bind specifically to the X or Y box.

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