CHROMOSOMAL POSITION EFFECTS IN CHICKEN LYSOZYME GENE TRANSGENIC MICEARE CORRELATED WITH SUPPRESSION OF DNASE-I HYPERSENSITIVE SITE FORMATION

The complete chicken lysozyme gene locus is expressed copy number depe ndently and at a high level in macrophages of transgenic mice. Gene ex pression independent of genomic position can only be achieved by the c oncerted action of all cis regulatory elements located on the lysozyme gene domain. Position independency of expression is lost if one essen tial cis regulatory region is deleted. Here we compared the DNase I hy persensitive site (DHS) pattern formed on the chromatin of position in dependently and position dependently expressed transgenes in order to assess the influence of deletions within the gene domain on active chr omatin formation. We demonstrate, that in position independently expre ssed transgene all DHSs are formed with the authentic relative frequen cy on all genes, This is not the case for position dependently express ed transgenes. Our results show that the formation of a DHS during cel lular differentiation does not occur autonomously. In case essential r egulatory elements of the chicken lysozyme gene domain are lacking, th e efficiency of DHS formation on remaining cis regulatory elements dur ing myeloid differentiation is reduced and influenced by the chromosom al position. Hence, no individual regulatory element on the lysozyme d omain is capable of organizing the chromatin structure of the whole lo cus in a dominant fashion.