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 development exhibiting a specific
chromatin structure with each differentiation state. Its
small size and the extensive characterization of its
cis-regulatory elements allows us to study even subtle
changes in chromatin structure of the entire gene
locus during transcriptional activation. Tissue-specific
and position independent expression of the lysozyme
locus in transgenic mice requires the cooperation of all
cis-regulatory elements. In order to elucidate further
the molecular basis of locus activation, we have
determined nucleosome positions within the complete
54-regulatory region of the chicken lysozyme locus in
chicken myeloid cell lines and transgenic mice. Each
cis-regulatory element develops its unique nucleosomal
structure and each one remodels chromatin
differently. The nucleosomal organization of the
endogenous gene in chicken cell lines and the transgene
in the mouse turned out to be identical, enabling
us to study the influence of cis-regulatory deletions on
the development of an active chromatin structure in
transgenic mice. Transgenes with a deletion of an
important cis-regulatory element show an impediment
in nucleosome reorganization as compared with the
complete lysozyme locus. We demonstrate that multicopy
transgene-clusters in position dependently
expressing mouse lines exhibit a heterogeneous
chromatin organization.