Hypermethylation of CpG islands in the mouse asparagine synthetase gene: relationship to asparaginase sensitivity in lymphoma cells. Partial methylation in normal cells

We have sequenced the promoter region of the murine asparagine synthetase g ene and examined its methylation profile in the CpG islands of L-asparagina se-sensitive 6C3HED cells (asparagine auxotrophs) and resistant variants (p rototrophs). In the former, complete methylation of the CpG island is corre lated with failure of expression of mRNA: cells of the latter possess both methylated and unmethylated alleles. as do cells of the intrinsically aspar agine-independent lines L1210 and EL4. A similar phenomenon was seen in nor mal splenic cells of adult mice. This was age related: no methylation was f ound in weanlings, but up to 45% of gene copies in animals 18 weeks or olde r were methylated. It was also tissue related, with methylation occurring r arely in liver cells. The relationship of these changes to oncogenesis is c onsidered. (C) 2001 Cancer Research Campaign.