Human matrix attachment regions insulate transgene expression from chromosomal position effects in Drosophila melanogaster.
Germ line transformation of white- Drosophila embryos with P-element vectors containing white expression cassettes results in flies with different eye color phenotypes due to position effects at the sites of transgene insertion. These position effects can be cured by specific DNA elements, such as the Drosophila scs and scs' elements, that have insulator activity in vivo. We have used this system to determine whether human matrix attachment regions (MARs) can function as insulator elements in vivo. Two different human MARs, from the apolipoprotein B and alpha1-antitrypsin loci, insulated white transgene expression from position effects in Drosophila melanogaster. Both elements reduced variability in transgene expression without enhancing levels of white gene expression. In contrast, expression of white transgenes containing human DNA segments without matrix-binding activity was highly variable in Drosophila transformants. These data indicate that human MARs can function as insulator elements in vivo.
Namciu
S J
SJ
Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109-1024, USA.
Blochlinger
K B
KB
Fournier
R E
RE
D018528:ATP-Binding Cassette Transporters; D000818:Animals; D030801:Animals, Genetically Modified; D001055:Apolipoproteins B / Q000235:genetics; D002875:Chromosomes / Q000502:physiology; D004247:DNA / Q000502:physiology*; D029721:Drosophila Proteins; D004331:Drosophila melanogaster; D005127:Eye Color / Q000235:genetics; D005136:Eye Proteins; D005786:Gene Expression Regulation; D006801:Humans; D019476:Insect Proteins / Q000235:genetics; D015530:Nuclear Matrix / Q000502:physiology*; D010641:Phenotype; D012168:Retinal Pigments / Q000235:genetics; D019076:Transgenes; D000515:alpha 1-Antitrypsin / Q000235:genetics
D018528:ATP-Binding Cassette Transporters; D001055:Apolipoproteins B; D029721:Drosophila Proteins; D005136:Eye Proteins; D019476:Insect Proteins; D012168:Retinal Pigments; D000515:alpha 1-Antitrypsin; C059254:w protein, Drosophila; D004247:DNA