DISSECTION OF THE LOCUS-CONTROL FUNCTION LOCATED ON THE CHICKEN LYSOZYME GENE DOMAIN IN TRANSGENIC MICE

The entire chicken lysozyme gene locus including all known cis-regulat ory sequences and the 5' and 3' matrix attachment sites defining the b orders of the DNase I sensitive chromatin domain, is expressed at a hi gh level and independent of its chromosomal position in macrophages of transgenic mice. It was concluded that the lysozyme gene locus carrie s a locus central function. We analysed several cis-regulatory deletio n mutants to investigate their influence on tissue specificity and lev el of expression. Position independent expression of the gene is lost whenever one of the upstream tissue specific enhancer regions is delet ed, although tissue specific expression is usually retained. Deletion of the domain border fragments has no influence on copy number depende ncy of expression. However, without these regions an increased inciden ce of ectopic expression is observed. This suggests that the domain bo rder fragments may help to suppress transgene expression in inappropri ate tissues. We conclude, that position independent expression of the lysozyme gene is not controlled by a single specific region of the loc us but is the result of the concerted action of several tissue specifi c upstream regulatory DNA elements with the promoter.