How does the location of a piece of DNA in the chromosome affect its expression? This is the question we are beginning to address through the use of beta-galactosidase tagged P-elements in Drosophila. P-elements are transposons, i.e. pieces of DNA flanked by ends, which insert relatively randomly in the genome. We have been using P-elements as vectors to make transgenic organisms to study regulatory elements of the developmentally important gene engrailed. In making transgenic organisms, a gene for eye color, white, is included in the P-element as a marker. Flies with uncolored eyes are injected with the P-element of interest, progeny with colored eyes contain the marker gene and therefore the P-element. In the course of our studies we found that engrailed sequences have the ability to turn off the expression of the marker gene. Further, this ability to turn off expression is influenced by the location of the P-element within the genome. We suspect that the promoter of the marker gene is interacting with regulatory sequences nearby, changing its level of expression. These studies may have relevance in the expression of retroviruses, such as HIV. Retroviruses also insert randomly in the genome and their level of expression is presumably influenced in some manner by the position of insertion. The level of viral transcription might bear some relationship to the severity of disease or the latency period.
