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METHYLATION PATTERN OF THE HLA‐DRα GENE IN HUMAN TISSUES
Author(s) -
Barbieri R.,
Nastruzzi C.,
Volinia S.,
Villa M.,
Piva R.,
Giacomini P.,
Natali P. G.,
Gambari R.
Publication year - 1990
Publication title -
international journal of immunogenetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.41
H-Index - 47
eISSN - 1744-313X
pISSN - 1744-3121
DOI - 10.1111/j.1744-313x.1990.tb00859.x
Subject(s) - methylation , human leukocyte antigen , gene , biology , genetics , dna methylation , computational biology , gene expression , antigen
SUMMARY 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 m CG→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.