Transcription activator-like effector hybrids for conditional control and rewiring of chromosomal transgene expression
The ability to conditionally rewire pathways in human cells holds great therapeutic potential. Transcription activator-like effectors (TALEs) are a class of naturally occurring specific DNA binding proteins that can be used to introduce targeted genome modifications or control gene expression. Here...
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| Format: | Online |
| Language: | English |
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Nature Publishing Group
2012
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3508452/ |
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pubmed-3508452 |
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oai_dc |
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pubmed-35084522012-11-28 Transcription activator-like effector hybrids for conditional control and rewiring of chromosomal transgene expression Li, Yi Moore, Richard Guinn, Michael Bleris, Leonidas Article The ability to conditionally rewire pathways in human cells holds great therapeutic potential. Transcription activator-like effectors (TALEs) are a class of naturally occurring specific DNA binding proteins that can be used to introduce targeted genome modifications or control gene expression. Here we present TALE hybrids engineered to respond to endogenous signals and capable of controlling transgenes by applying a predetermined and tunable action at the single-cell level. Specifically, we first demonstrate that combinations of TALEs can be used to modulate the expression of stably integrated genes in kidney cells. We then introduce a general purpose two-hybrid approach that can be customized to regulate the function of any TALE either using effector molecules or a heterodimerization reaction. Finally, we demonstrate the successful interface of TALEs to specific endogenous signals, namely hypoxia signaling and microRNAs, essentially closing the loop between cellular information and chromosomal transgene expression. Nature Publishing Group 2012-11-28 /pmc/articles/PMC3508452/ /pubmed/23193439 http://dx.doi.org/10.1038/srep00897 Text en Copyright © 2012, Macmillan Publishers Limited. All rights reserved http://creativecommons.org/licenses/by-nc-nd/3.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/ |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Li, Yi Moore, Richard Guinn, Michael Bleris, Leonidas |
| spellingShingle |
Li, Yi Moore, Richard Guinn, Michael Bleris, Leonidas Transcription activator-like effector hybrids for conditional control and rewiring of chromosomal transgene expression |
| author_facet |
Li, Yi Moore, Richard Guinn, Michael Bleris, Leonidas |
| author_sort |
Li, Yi |
| title |
Transcription activator-like effector hybrids for conditional control and rewiring of chromosomal transgene expression |
| title_short |
Transcription activator-like effector hybrids for conditional control and rewiring of chromosomal transgene expression |
| title_full |
Transcription activator-like effector hybrids for conditional control and rewiring of chromosomal transgene expression |
| title_fullStr |
Transcription activator-like effector hybrids for conditional control and rewiring of chromosomal transgene expression |
| title_full_unstemmed |
Transcription activator-like effector hybrids for conditional control and rewiring of chromosomal transgene expression |
| title_sort |
transcription activator-like effector hybrids for conditional control and rewiring of chromosomal transgene expression |
| description |
The ability to conditionally rewire pathways in human cells holds great therapeutic potential. Transcription activator-like effectors (TALEs) are a class of naturally occurring specific DNA binding proteins that can be used to introduce targeted genome modifications or control gene expression. Here we present TALE hybrids engineered to respond to endogenous signals and capable of controlling transgenes by applying a predetermined and tunable action at the single-cell level. Specifically, we first demonstrate that combinations of TALEs can be used to modulate the expression of stably integrated genes in kidney cells. We then introduce a general purpose two-hybrid approach that can be customized to regulate the function of any TALE either using effector molecules or a heterodimerization reaction. Finally, we demonstrate the successful interface of TALEs to specific endogenous signals, namely hypoxia signaling and microRNAs, essentially closing the loop between cellular information and chromosomal transgene expression. |
| publisher |
Nature Publishing Group |
| publishDate |
2012 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3508452/ |
| _version_ |
1611936044829114368 |