Methylation pattern of the HLA-DR alpha gene in human tissues.
The CCGG and GCGC sites of the human HLA-DR alpha 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-DR alpha gene can be transcribed even though extensively methylated. The only exception to the hypermethylated state of the HLA-DR alpha 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-DR alpha 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-DR alpha MRNA. On the other hand, the selective pressure to maintain unaltered the methylated CG dinucleotides in the coding regions of the HLA-DR alpha 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-DR alpha genomic sequences indicates that variations of the CpG dinucleotides occur only in the non-coding portions of the HLA-DR alpha gene.
Barbieri
R
R
Istituto di Chimica Biologica, Ferrara, Italy.
Nastruzzi
C
C
Volinia
S
S
Villa
M
M
Piva
R
R
Giacomini
P
P
Natali
P G
PG
Gambari
R
R
D001483:Base Sequence; D002460:Cell Line; D004247:DNA / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005802:Genes, MHC Class II; D006684:HLA-DR Antigens / Q000235:genetics*; D006801:Humans; D007962:Leukocytes / Q000378:metabolism; D008297:Male; D008745:Methylation; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics / Q000648:ultrastructure; D014018:Tissue Distribution
D006684:HLA-DR Antigens; D012333:RNA, Messenger; D004247:DNA