Position effect variegation and imprinting of transgenes in lymphocytes.
Sequences proximal to transgene integration sites are able to deregulate transgene expression resulting in complex position effect phenotypes. In addition, transgenes integrated as repeated arrays are susceptible to repeat-induced gene silencing. Using a Cre recombinase-based system we have addressed the influence of transgene copy number (CN) on expression of hCD2 transgenes. CN reduction resulted in a decrease, increase or no effect on variegation depending upon the site of integration. This finding argues that repeat-induced gene silencing is not the principle cause of hCD2 transgene variegation. These results also suggest that having more transgene copies can be beneficial at some integration sites. The transgenic lines examined in this report also exhibited a form of imprinting, which was manifested by decreased levels of expression and increased levels of variegation, upon maternal transmission; and this correlated with DNA hypermethylation and a reduction in epigenetic chromatin modifications normally associated with active genes.
Williams
Adam
A
Division of Molecular Immunology, The National Institute for Medical Research, London, NW71AA, UK.
Harker
Nicola
N
Ktistaki
Eleni
E
Veiga-Fernandes
Henrique
H
Roderick
Kathleen
K
Tolaini
Mauro
M
Norton
Trisha
T
Williams
Keith
K
Kioussis
Dimitris
D
D000818:Animals; D018801:CD2 Antigens / Q000235:genetics* / Q000378:metabolism; D047369:Chromatin Immunoprecipitation; D019175:DNA Methylation; D005434:Flow Cytometry; D018628:Gene Dosage; D020868:Gene Silencing; D018392:Genomic Imprinting; D006801:Humans; D019901:Locus Control Region; D051379:Mice; D008822:Mice, Transgenic; D013601:T-Lymphocytes / Q000276:immunology; D019076:Transgenes
D018801:CD2 Antigens