Lack of correlation between hypomethylation and expression of the HLA-DR alpha gene

DNA methylation at the 5'-CCGG-3' sites of the HLA-DR alpha gene and relative flanking regions has been analyzed by Msp I and Hpa II enzymatic digestion in order to determine whether a correlation exists between DNA methylation and transcription of the HLA-DR alpha gene. Unexpectedly, and in contrast to the behavior of most eukaryotic genes, no positive correlation was found between hypomethylation and expression. In fact, HLA-DR alpha appears to be fully unmethylated at Msp I/Hpa II sites in K562 cells, not expressing DR molecules, and to exhibit a high degree of methylation in Colo 38 cells, which actively transcribe the gene. The unorthodox behavior of HLA-DR alpha is not unique to melanoma or erythroid cells since a similar, positive correlation between methylation and expression also exists when this analysis is extended to cell lines belonging to other histotypes.