Chromatin structure of transcriptionally active and inactive human c-myc alleles

To help elucidate the mechanism of regulation of the c-myc gene we have characterised the DNase I hypersensitive sites around this gene in the human promyelocytic leukaemia cell line HL60, which carries amplified c-myc, and in Ramos, a Burkitt's lymphoma cell line with a translocation close to exon 1 of c-myc. Although dividing HL60 cells display a pattern of DNase I hypersensitive sites which is similar to that of previously described c-myc genes in B cells (lymphoblastoid and Burkitt's lymphoma), changes were found in DNase I hypersensitive sites upon differentiation of the HL60 cell line (accompanied by decreased c-myc transcription). Lack of c-myc transcription coincides with the loss of several DNase I hypersensitive sites and the reduction in intensity of a further site. A similar pattern was also seen in the inactive allele of the Burkitt's lymphoma cell line Ramos. A striking feature of both differentiated HL60 cells and of the inactive allele in Ramos is the quantitative maintenance of a DNase I hypersensitive site which occurs approximately 2.5 kb upstream of the c-myc gene promoters.