The –3.9 kb DHS of the chicken lysozyme locus harbors an enhancer element with unusual chromatin reorganizing activity

Tissue specific regulation of the chicken lysozyme locus is achieved by a combination of positive and negative cis-regulatory elements. Here we describe the molecular characterization of a newly discovered enhancer element located −3.9 kb upstream of the transcription start. The −3.9 kb enhancer is activated early in macrophage differentiation, as indicated by chromatin reorganization in macrophage precursor cells. Interestingly, enhancer activation leads to nucleosome phasing. Tissue specificity of expression is achieved by a combination of 5′-sequences with ubiquitous enhancer activity and 3′-flanking sequences. The 5′-half contains binding sites for members of the nuclear factor I transcription family and a yet unknown protein. We could show by in vivo footprinting that the ubiquitously expressed factors occupy their binding sites only in lysozyme expressing cells. We conclude that a specific chromatin architecture may be responsible for the differential activity of the enhancer.