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dc.contributor.authorMüller-Kuller, Utaen_US
dc.contributor.authorAckermann, Maniaen_US
dc.contributor.authorKolodziej, Stephanen_US
dc.contributor.authorBrendel, Christianen_US
dc.contributor.authorFritsch, Jessicaen_US
dc.contributor.authorLachmann, Nicoen_US
dc.contributor.authorKunkel, Hanaen_US
dc.contributor.authorLausen, Jörnen_US
dc.contributor.authorSchambach, Axelen_US
dc.contributor.authorMoritz, Thomasen_US
dc.contributor.authorGrez, Manuelen_US
dc.date.accessioned2015-04-01T15:30:21Z
dc.date.issued2015en_US
dc.identifier.citationMüller-Kuller, U., M. Ackermann, S. Kolodziej, C. Brendel, J. Fritsch, N. Lachmann, H. Kunkel, et al. 2015. “A minimal ubiquitous chromatin opening element (UCOE) effectively prevents silencing of juxtaposed heterologous promoters by epigenetic remodeling in multipotent and pluripotent stem cells.” Nucleic Acids Research 43 (3): 1577-1592. doi:10.1093/nar/gkv019. http://dx.doi.org/10.1093/nar/gkv019.en
dc.identifier.issn0305-1048en
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:14351275
dc.description.abstractEpigenetic silencing of transgene expression represents a major obstacle for the efficient genetic modification of multipotent and pluripotent stem cells. We and others have demonstrated that a 1.5 kb methylation-free CpG island from the human HNRPA2B1-CBX3 housekeeping genes (A2UCOE) effectively prevents transgene silencing and variegation in cell lines, multipotent and pluripotent stem cells, and their differentiated progeny. However, the bidirectional promoter activity of this element may disturb expression of neighboring genes. Furthermore, the epigenetic basis underlying the anti-silencing effect of the UCOE on juxtaposed promoters has been only partially explored. In this study we removed the HNRPA2B1 moiety from the A2UCOE and demonstrate efficient anti-silencing properties also for a minimal 0.7 kb element containing merely the CBX3 promoter. This DNA element largely prevents silencing of viral and tissue-specific promoters in multipotent and pluripotent stem cells. The protective activity of CBX3 was associated with reduced promoter CpG-methylation, decreased levels of repressive and increased levels of active histone marks. Moreover, the anti-silencing effect of CBX3 was locally restricted and when linked to tissue-specific promoters did not activate transcription in off target cells. Thus, CBX3 is a highly attractive element for sustained, tissue-specific and copy-number dependent transgene expression in vitro and in vivo.en
dc.language.isoen_USen
dc.publisherOxford University Pressen
dc.relation.isversionofdoi:10.1093/nar/gkv019en
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC4330381/pdf/en
dash.licenseLAAen_US
dc.titleA minimal ubiquitous chromatin opening element (UCOE) effectively prevents silencing of juxtaposed heterologous promoters by epigenetic remodeling in multipotent and pluripotent stem cellsen
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journalNucleic Acids Researchen
dash.depositing.authorSchambach, Axelen_US
dc.date.available2015-04-01T15:30:21Z
dc.identifier.doi10.1093/nar/gkv019*
dash.authorsorderedfalse
dash.contributor.affiliatedSchambach, Axel


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