Blackwell Publishing Journal Backfiles 1879-2005
The CCGG and GCGC sites of the human HLA-DRα gene are hypermethylated in human tissues (including B-lymphocytes, T-lymphocytes, muscle, brain, sperm, skin, kidney, suprarenal and mammary glands) and three B-lymphoid cell lines. Therefore, the HLA-DRα gene can be transcribed even though extensively methylated. The only exception to the hypermethylated state of the HLA-DRα gene is represented by one or both of the two HhaI sites (H1 and H2) localized in the 5’portion of the gene. Analysis of the computer-generated secondary structure of the HLA-DRα mRNA suggests that the H1 and H2 sites belong to a region (5′-GAGCGCCCA-3′/5′-UGAGCGCUC-3′) exhibiting extensive base pairing. Therefore, unmethylation of these CG sites can contribute in preventing mCG→TG/CA changes in this region, which would lead to extensive alterations of the secondary structure of the 5’portion of the HLA-DRα MRNA.On the other hand, the selective pressure to maintain unaltered the methylated CG dinucleotides in the coding regions of the HLA-DRα gene could be due to codon restrictions, since the majority of the methylation-related CG→TG or CG→CA variations would generate aminoacid changes.Accordingly, the analysis of different HLA-DRα genomic sequences indicates that variations of the CpG dinucleotides occur only in the non-coding portions of the HLA-DRα gene.
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