THE HUMAN LYSOZYME GENE UNDERGOES STEPWISE DEMETHYLATION DURING PHAGOCYTE MATURATION

The lysozyme (LZM) gene provides a very useful model for studies of ph agocyte maturation, because its protein synthesis is increased during myelopoiesis and thus most abundant in terminally differentiated and a ctivated phagoyctes. LZM gene expression and DNA methylation were exam ined in various normal and transformed hematopoietic cells. Two shifts toward LZM gene demethylation coincided with upregulation of expressi on: activation of expression in myeloid precursor cells was associated with significant demethylation at a CpG dinucleotide within an Alo re peat in the 5' flanking region; high-level expression in different typ es of mature phagocytic cells was associated with complete demethylati on at two additional, intragenic CpG sites contained in Alo sequences. The possibility that methylation changes occurring within the 5' regi on of the human lysozyme gene could be involved in the transcription o f this gene is discussed, as well as a possible role for demethylation in the maintenance of distinct maturation stages during phagocyte dev elopment.