The 5' flanking region of the rat LAP (C/EBP beta) gene can direct high-level, position-independent, copy number-dependent expression in multiple tissues in transgenic mice.
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/EBP beta) directs position-independent, copy number-dependent expression in transgenic-mouse livers. Concomitantly, the DNAse I hypersensitivity 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 cis-linked LCR-like element has been associated.
Talbot
D
D
Department of Molecular Biology, University of Geneva, Switzerland.
Descombes
P
P
Schibler
U
U
D000818:Animals; D001483:Base Sequence; D022762:CCAAT-Enhancer-Binding Proteins; D002843:Chromatin / Q000378:metabolism; D004247:DNA; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics*; D003850:Deoxyribonuclease I; D005786:Gene Expression Regulation; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics*; D009928:Organ Specificity / Q000235:genetics; D011401:Promoter Regions, Genetic; D051381:Rats; D012045:Regulatory Sequences, Nucleic Acid; D015183:Restriction Mapping; D012260:Ribonucleases / Q000378:metabolism; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics*
D022762:CCAAT-Enhancer-Binding Proteins; D002843:Chromatin; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors; D004247:DNA; D012260:Ribonucleases; D003850:Deoxyribonuclease I