title: Position effect variegation and imprinting of transgenes in lymphocytes.
abstract: 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.
authors.affiliation: Division of Molecular Immunology, The National Institute for Medical Research, London, NW71AA, UK.
authors.forename: Adam
authors.initials: A
authors.lastname: Williams
authors.forename: Nicola
authors.initials: N
authors.lastname: Harker
authors.forename: Eleni
authors.initials: E
authors.lastname: Ktistaki
authors.forename: Henrique
authors.initials: H
authors.lastname: Veiga-Fernandes
authors.forename: Kathleen
authors.initials: K
authors.lastname: Roderick
authors.forename: Mauro
authors.initials: M
authors.lastname: Tolaini
authors.forename: Trisha
authors.initials: T
authors.lastname: Norton
authors.forename: Keith
authors.initials: K
authors.lastname: Williams
authors.forename: Dimitris
authors.initials: D
authors.lastname: Kioussis
mesh_terms: 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
chemical_list: D018801:CD2 Antigens