Nucleic Acids Research, 1994, Vol. 22, No. 20 4202-4210
© 1994
MOLECULAR BIOLOGY |
Dissection of the locus control function located on the chicken lysozyme gene domain in transgenic mice
Institut fur Biologie III der Universitat Freiburg SchanzlestraRe 1, D-79104 Freiburg, Germany 1National Institute for Medical Research The Ridgeway, Mill Hill, London NW7 1AA, UK
*To whom correspondence should be addressed
Received June 20, 1994. Revised September 12, 1994. Accepted September 12, 1994.
The entire chicken lysozyme gene locus including all known cis-regulatory sequences and the 5' and 3' matrix attachment sites defining the borders of the DNase I sensitive chromatin domain, is expressed at a high level and independent of its chromosomal position in macrophages of transgenic mice. It was concluded that the lysozyme gene locus carries a locus control function. We analysed several cis-regulatory deletion mutants to investigate their influence on tissue specificity and level of expression. Position independent expression of the gene is lost whenever one of the upstream tissue specific enhancer regions is deleted, although tissue specific expression is usually retained. Deletion of the domain border fragments has no influence on copy number dependency of expression. However, without these regions an increased incidence of ectopic expression is observed. This suggests that the domain border fragments may help to suppress transgene expression in inappropriate tissues. We conclude, that position independent expression of the lysozyme gene is not controlled by a single specific region of the locus but is the result of the concerted action of several tissue specific upstream regulatory DNA elements with the promote.
$Present address: Department of Cell Biology and Genetics, Erasmus University Rotterdam, dr. Molewaterplein 50, 3000 DR Rotterdam, The Netherland
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