DYNAMIC CHANGES IN THE CHROMATIN OF THE CHICKEN LYSOZYME GENE DOMAIN DURING DIFFERENTIATION OF MULTIPOTENT PROGENITORS TO MACROPHAGES

The chicken lysozyme locus is regulated in oviduct and macrophages by a complex set of well-characterized cis-regulatory DNA elements. We de termined the DNase I hypersensitive chromatin site pattern of the chro matin of the lysozyme locus in retrovirally transformed cell lines rep resenting different stages of myelomonocytic cell differentiation. In the transformed multipotent progenitor stage and in erythroblasts, onl y a DNase I hypersensitive chromatin site at a silencer element locate d -2.4 kb upstream of the transcriptional start site is present. At th e myeloblast stage DNase I hypersensitive chromatin sites are formed b oth at the distal enhancer located at -6.1 kb and at the promoter. Lat er in differentiation, at the monocytic stage, a second DNase I hypers ensitive chromatin site appears at the medial enhancer located at -2.7 kb. Parallel with DNase I hypersensitive chromatin site formation at the medial enhancer, the DNase I hypersensitive chromatin site at the silencer element disappears. These chromatin rearrangements correlate with the mRNA expression of the gene that is undetectable in multipote nt progenitors and maximal in a lipopolysaccharide-stimulated monocyte cell line. Our results show that the chromatin structure and the tran scriptional activity of the gene are tightly coupled during commitment and maturation of the myelomonocytic lineage.