GENOMIC POSITION EFFECTS LEAD TO AN INEFFICIENT REORGANIZATION OF NUCLEOSOMES IN THE 5'-REGULATORY REGION OF THE CHICKEN LYSOZYME LOCUS IN TRANSGENIC MICE

The chicken lysozyme locus is gradually activated during macrophage de velopment exhibiting a specific chromatin structure with each differen tiation state. Its small size and the extensive characterization of it s cis-regulatory elements allows us to study even subtle changes in ch romatin structure of the entire gene locus during transcriptional acti vation. Tissue-specific and position independent expression of the lys ozyme locus in transgenic mice requires the cooperation of all cis-reg ulatory elements. In order to elucidate further the molecular basis of locus activation, we have determined nucleosome positions within the complete 5'-regulatory region of the chicken lysozyme locus in chicken myeloid cell lines and transgenic mice. Each cis-regulatory element d evelops its unique nucleosomal structure and each one remodels chromat in differently. The nucleosomal organization of the endogenous gene in chicken cell lines and the transgene in the mouse turned out to be id entical, enabling us to study the influence of cis-regulatory deletion s on the development of an active chromatin structure in transgenic mi ce. Transgenes with a deletion of an important cis-regulatory element shaw an impediment in nucleosome reorganization as compared with the c omplete lysozyme locus. We demonstrate that multicopy transgene-cluste rs in position dependently expressing mouse lines exhibit heterogeneou s chromatin organization.