Please use this identifier to cite or link to this item:
|Title:||Recognition and suppression of transfected plasmids by protein ZNF511-PRAP1, a potential molecular barrier to transgene expression||Authors:||Qiu, G.-H.
|Issue Date:||Aug-2011||Citation:||Qiu, G.-H., Leung, C.H.-W., Yun, T., Xie, X., Laban, M., Hooi, S.C. (2011-08). Recognition and suppression of transfected plasmids by protein ZNF511-PRAP1, a potential molecular barrier to transgene expression. Molecular Therapy 19 (8) : 1478-1486. ScholarBank@NUS Repository. https://doi.org/10.1038/mt.2011.80||Abstract:||Nonviral vectors present considerable advantages over viral counterparts in gene transfer. However, the poor expression efficiency of the transfected genes poses a challenge for their use in gene therapy, primarily due to the inability of these vectors to overcome various barriers, including the biological barriers. Here, we report that ZNF511-PRAP1 may be involved in the recognition and inactivation of transfected plasmids. ZNF511-PRAP1 is induced by transfection of plasmid DNA and suppresses the transcription of transfected plasmids. It binds directly to the p21 promoter in transfected plasmids but not the endogenous counterpart. Similarly, ZNF511-PRAP1 suppresses the expression of the green fluorescent protein reporter gene on transiently transfected plasmids but not an integrated red fluorescence reporter gene with the same cytomegalovirus (CMV) promoter. Therefore, ZNF511-PRAP1 is able to differentiate between exogenous/nonintegrated and endogenous/integrated DNA. The suppression by ZNF511-PRAP1 is independent of DNA methylation and can be abolished by trichostatin A (TSA) treatment and knockdown of HDAC2 and/or ZNF511-PRAP1. Furthermore, ZNF511-PRAP1 interacts directly with HDAC2. Our results revealed that transfected plasmids are recognized by ZNF511-PRAP1 and suppressed by a repressor complex comprising ZNF511-PRAP1 and HDAC2 and suggest that ZNF511-PRAP1 could play a role as a potential molecular barrier in nonviral transgene expression. © The American Society of Gene & Cell Therapy.||Source Title:||Molecular Therapy||URI:||http://scholarbank.nus.edu.sg/handle/10635/125670||ISSN:||15250016||DOI:||10.1038/mt.2011.80|
|Appears in Collections:||Staff Publications|
Show full item record
Files in This Item:
There are no files associated with this item.
checked on Oct 13, 2019
WEB OF SCIENCETM
checked on Oct 4, 2019
checked on Oct 11, 2019
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.