Tissue-specific undermethylation of DNA sequences at the 5' end of the human apolipoprotein B gene.

The methylation-sensitive restriction endonucleases HpaII and HhaI and the methylation-insensitive enzyme MspI were used to examine the methylation status of the 5' end of the human apolipoprotein B gene in cells in which the gene is transcriptionally active, such as HepG2 and CaCo-2 cells, and in HeLa cells, which do not express the gene. Several CCGG and GCGC sequences present in the region from -899 to +121 relative to the transcriptional start of the gene were undermethylated in HepG2 and CaCo-2 cells but methylated in HeLa cells. Because the region between -899 and +121 had previously been shown to exhibit tissue-specific promoter activity and to contain many DNaseI- and micrococcal nuclease-hypersensitive sites (Levy-Wilson, B., Fortier, C., Blackhart, B.D., and McCarthy, B.J. (1988) Mol. Cell. Biol. 8, 71-80), the current results suggest a correlation between undermethylation and nuclease sensitivity at the 5' end of the apolipoprotein B gene and expression of the gene.