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Publication : Position effect variegation and imprinting of transgenes in lymphocytes.

First Author  Williams A Year  2008
Journal  Nucleic Acids Res Volume  36
Issue  7 Pages  2320-9
PubMed ID  18296483 Mgi Jnum  J:172154
Mgi Id  MGI:5004767 Doi  10.1093/nar/gkn085
Citation  Williams A, et al. (2008) Position effect variegation and imprinting of transgenes in lymphocytes. Nucleic Acids Res 36(7):2320-9
abstractText  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.
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