Granulocytic differentiation of HL-60 cells is not regulated by DNA de novo methylation.

DNA cytosine methylation and transcription of specific genes are inversely correlated. In granulocytic differentiation of HL-60 cells there is a distinct down regulation of the c-myc proto-oncogene expression, which is probably a causal mechanism. With differentiation of HL-60 cells we found no restriction enzyme fragment length polymorphism (RFLP) within the c-myc proto-oncogene, which indicates that there is no loss of regulatory elements (e.g., TATAA boxes within the first exon). Furthermore, we found no de novo methylation in this region. Methylation of other DNA regions, which could influence c-myc expression, is also not necessary for differentiation, as was shown by inhibition of DNA methylase. L-Ethionine and S-adenosyl-L-homocysteine are both potent inhibitors of DNA methylase and do not influence proliferation of HL-60 cells, as shown by FACS analysis.