Absence of in vivo DNA-protein interactions in the DQA2 and DQB2 promoter regions.
The DQ subregion of the human major histocompatibility complex (HLA) contains two pairs of loci: the DQA1/B1 genes (hereafter called DQ1), coding for the DQ molecules, and the DQA2/B2 pseudogenes (hereafter called DQ2). These pseudogenes are highly homologous to the functional DQ1 genes and they have no apparent abnormal features in their sequences that could prevent their activity. Only recently a low expression of the DQA2 gene has been observed whereas the DQB2 transcript was never found. The comparison between the DQ1 and DQ2 regulatory sequences revealed several differences in their W, X, and Y cis-acting elements. To examine the DNA/protein interactions in the DQ promoter regions, we performed in vivo footprinting experiments. Whereas the functional DQ1 loci showed a series of DNA-protein contact points in the X and Y boxes, the promoters of the DQ2 pseudogenes displayed an unoccupied phenotype. These findings suggest that the very low level of DQA2 expression and the apparent lack of DQB2 activity are caused by the reduced binding affinity of specific transcription factors.
Indovina
P
P
Dipartimento di Medicina Sperimentale e Patologia, Università "La Sapienza,", Rome, Italy.
Megiorni
F
F
Fontemaggi
G
G
Coni
P
P
Mora
B
B
Mazzilli
M C
MC
D002460:Cell Line; D004247:DNA / Q000378:metabolism; D006683:HLA-DQ Antigens / Q000235:genetics*; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; D006801:Humans; D011401:Promoter Regions, Genetic; D011506:Proteins / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*
D006683:HLA-DQ Antigens; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; C069050:HLA-DQA1 antigen; C103596:HLA-DQA2 antigen; C069051:HLA-DQB1 antigen; C040626:HLA-Dx antigen; D011506:Proteins; D014157:Transcription Factors; D004247:DNA