Zhang, F;
Santilli, G;
Thrasher, AJ;
(2017)
Characterization of a core region in the A2UCOE that confers effective anti-silencing activity.
Scientific Reports
, 7
, Article 10213. 10.1038/s41598-017-10222-3.
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Abstract
We have previously shown that reliability of the A2UCOE in driving transgene expression can be attributed to its resistance to DNA methylation, and its ability to confer this property to linked regulatory sequences. In order to gain a better understanding of how resistance to DNA methylation from the A2UCOE is conferred, and whether the anti-silencing effect from the A2UCOE is confined within a core region, we evaluated the anti-silencing effect of different sub-domains. We found that maximal epigenetic regulatory activity was contained within a 455 bp element derived from the CBX3 region when tested in the context of a lentiviral vector in murine embryonic stem (ES) cells and human inducible pluripotent stem (iPS) cells. This region possessed an active chromatin signature, and operated effectively in cis to protect linked heterologous regulatory elements from methylation, thereby conferring stable transgene expression. Defined UCOE elements may be particularly useful for use in vectors where gene expression is desired in methylation-prone chromatin environments such as those encountered in pluripotent stem cells.
| Type: | Article |
|---|---|
| Title: | Characterization of a core region in the A2UCOE that confers effective anti-silencing activity |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1038/s41598-017-10222-3 |
| Publisher version: | http://dx.doi.org/10.1038/s41598-017-10222-3 |
| Language: | English |
| Additional information: | Open Access: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Infection, Immunity and Inflammation Dept |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1573122 |
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