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 anima ls is usually subject to the position of integration into the host chr omatin. We have discovered that a 2.8kbp fragment flanking the rat gen e encoding the transcription factor LAP (C/EBPbeta) directs position-i ndependent, copy number-dependent expression in transgenic-mouse liver s. Concomitantly, the DNAse I hypersensitivity pattern normally observ ed in the liver is established in the integrated transgene construct d emonstrating that this region is capable of creating chromatin structu res equivalent to the endogenous situation. These observations are rem iniscent of the locus control regions (LCR) described for several gene s. Additionally, this LAP element functions with both intron-less and intron-containing genes. The tissue specificity of this element, howev er, is not restricted to liver. The 2.8kbp region is capable of allowi ng position-independent, copy number-dependent expression in brain, ki dney, heart, spleen, and lung, but in a construct-dependent manner. Th is is, to our knowledge, the first transcription factor gene with whic h a cis-linked LCR-like element has been associated.