Chromatin structural analysis of the 5' end and contiguous flanking region of the myeloperoxidase gene.

Myeloperoxidase (MPO) synthesis is known to be associated with the promyelocyte stage of myeloid differentiation. In particular the downregulation of MPO gene transcription is associated with myeloid cell maturation. We examined the changes in the deoxyribonuclease I hypersensitive sites within the 5' end of the MPO gene and its 5' flanking region during dimethyl sulfoxide (DMSO)-induced differentiation of HL-60 cells to determine the changes in chromatin structure that accompany this process. The locations of hypersensitive sites surrounding the 5' end of the gene in proliferating, uninduced cells were determined: three were observed in the 5' flanking region and one within the gene. Progressive changes in all sites accompanied the downregulation of MPO transcription after treatment with DMSO. No evidence of hypersensitivity was observed in the chromatin region examined after 8 days of DMSO exposure. The results provide an example of the changes that occur in the chromatin structure of a gene as it is inactivated during differentiation.