Nucleic Acids Research, 1994, Vol. 22, No. 5 756-766
© 1994
MOLECULAR BIOLOGY |
The 5' flanking region of the rat LAP (C/EBPß) gene can direct high-level, position-independent, copy number dependent expression in multiple tissues in transgenic mice
Department of Molecular Biology, University of Geneva 30 Quai E. Ansermet, Geneva, CH1211, Switzerland
* TO whom correspondence should be addressed
Received December 10, 1993. Revised February 9, 1994. Accepted February 9, 1994.
The efficiency and tissue-specificity of transgene expression in animals Is usually subject to the position of integration Into the host chromatin. We have discovered that a 2.8kbp fragment flanking the rat gene encoding the transcription factor LAP (C/EBPß) directs position-independent, copy number-dependent expression in transgenic-mouse livers. Concomitantly, the DNAse I hypersensltivlty pattern normally observed in the liver is established in the integrated transgene construct demonstrating that this region is capable of creating chromatin structures equivalent to the endogenous situation. These observations are reminiscent of the locus control regions (LCR) described for several genes. Additionally, this LAP element functions with both Intron-less and intron-containing genes. The tissue specificity of this element, however, is not restricted to liver. The 2.8kbp region is capable of allowing position-independent, copy number dependent expression in brain, kidney, heart, spleen, and lung, but In a construct-dependent manner. This is, to our knowledge, the first transcription factor gene with which a cls-linked LCR-like element has been associated.
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