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

大鼠LAP(C/EBPβ)基因的5'侧翼区可在转基因小鼠的多种组织中指导高水平、位置非依赖性、拷贝数依赖性的表达。

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Abstract

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.

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