Locus- and allele-specific DNA-protein interactions in the HLA-DQB1 X box

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Abstract
Expression of MHC class II genes is regulated by a complex series of protein-DNA interactions which lead to the initiation of transcription. Although the different MHC class II loci are generally coordinately expressed, important differences in expression can be seen among loci and among individual alleles. The major sites of transcriptional control in the human MHC consist of several highly conserved nucleotide sequence elements located upstream of each MHC class II gene. We have analyzed the interlocus and interallelic variation in one of these key regulatory regions of the HLA-DQB1 promoter, the X box, and identified several sites of protein-DNA interaction. Two protein-DNA complexes were found which differ between the DQ and DR loci as well as two distinct complexes which differed between DQ alleles. These nuclear protein-X box interactions are likely to influence the differential expression of the MHC class II loci and alleles in tissue-specific or developmentally regulated pathways.