Chromatin structure of the c-myc gene in HL-60 cells during alterations of transcriptional activity.

ABSTRACT

HL-60 cells have an elevated level of cellular myc RNA due to an amplified c-myc gene. Subsequent to chemically induced differentiation of HL-60 cells, both cellular myc RNA levels (Grosso, L. E., and Pitot, H. C., Biochem. Biophys. Res. Commun., 119 473, 1984) and myc-specific transcription decrease (Grosso, L. E., and Pitot, H. C., Cancer Res., 45 847-850, 1985). We have compared the primary DNA structure, DNA methylation, and S1 nuclease sensitivity of the myc protooncogene in HL-60 cells before and after chemically induced differentiation. We find no change in the structure or methylation of the c-myc gene. The protooncogene is hypomethylated at CCGG sequences in the 5' region but is extensively methylated at sites detected by sequences homologous to the 3' exon or 3' flanking sequences. Four S1 nuclease-sensitive sites are detected prior to differentiation. After the induction of either myeloid or monocytic differentiation, three of the S1 nuclease-sensitive sites are present. The presence of the fourth S1 nuclease-sensitive site correlates with the transcriptional activity of this gene.