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Article: Comparison of TALE designer transcription factors and the CRISPR/dCas9 in regulation of gene expression by targeting enhancers

TitleComparison of TALE designer transcription factors and the CRISPR/dCas9 in regulation of gene expression by targeting enhancers
Authors
Issue Date2014
Citation
Nucleic Acids Research, 2014, v. 42, n. 20 How to Cite?
Abstract© The Author(s) 2014. The transcription activator-like effectors (TALEs) and the RNA-guided clustered regularly interspaced short palindromic repeat (CRISPR) associated protein (Cas9) utlil ize distinct molecular mechanisms in targeting site recognition. The two proteins can be modified to carry additional functional domains to regulate expression of genomic loci in mammalian cells. In this study, we have compared the two systems in activation and suppression of the Oct4 and Nanog loci by targeting their enhancers. Although both are able to efficiently activate the luciferase reporters, the CRISPR/dCas9 system is much less potent in activating the endogenous loci and in the application of reprogramming somatic cells to iPS cells. Nevertheless, repression by CRISPR/dCas9 is comparable to or even better than TALE repressors. We demonstrated that dCas9 protein binding results in significant physical interference to binding of native transcription factors at enhancer, less efficient active histone markers induction or recruitment of activating complexes in gene activation. This study thus highlighted the merits and drawbacks of transcription regulation by each system. A combined approach of TALEs and CRISPR/dCas9 should provide an optimized solution to regulate genomic loci and to study genetic elements such as enhancers in biological processes including somatic cell reprogramming and guided differentiation.
Persistent Identifierhttp://hdl.handle.net/10722/249124
ISSN
2023 Impact Factor: 16.6
2023 SCImago Journal Rankings: 7.048
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorGao, Xuefei-
dc.contributor.authorTsang, Jason C.H.-
dc.contributor.authorGaba, Fortis-
dc.contributor.authorWu, Donghai-
dc.contributor.authorLu, Liming-
dc.contributor.authorLiu, Pentao-
dc.date.accessioned2017-10-27T05:59:10Z-
dc.date.available2017-10-27T05:59:10Z-
dc.date.issued2014-
dc.identifier.citationNucleic Acids Research, 2014, v. 42, n. 20-
dc.identifier.issn0305-1048-
dc.identifier.urihttp://hdl.handle.net/10722/249124-
dc.description.abstract© The Author(s) 2014. The transcription activator-like effectors (TALEs) and the RNA-guided clustered regularly interspaced short palindromic repeat (CRISPR) associated protein (Cas9) utlil ize distinct molecular mechanisms in targeting site recognition. The two proteins can be modified to carry additional functional domains to regulate expression of genomic loci in mammalian cells. In this study, we have compared the two systems in activation and suppression of the Oct4 and Nanog loci by targeting their enhancers. Although both are able to efficiently activate the luciferase reporters, the CRISPR/dCas9 system is much less potent in activating the endogenous loci and in the application of reprogramming somatic cells to iPS cells. Nevertheless, repression by CRISPR/dCas9 is comparable to or even better than TALE repressors. We demonstrated that dCas9 protein binding results in significant physical interference to binding of native transcription factors at enhancer, less efficient active histone markers induction or recruitment of activating complexes in gene activation. This study thus highlighted the merits and drawbacks of transcription regulation by each system. A combined approach of TALEs and CRISPR/dCas9 should provide an optimized solution to regulate genomic loci and to study genetic elements such as enhancers in biological processes including somatic cell reprogramming and guided differentiation.-
dc.languageeng-
dc.relation.ispartofNucleic Acids Research-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.titleComparison of TALE designer transcription factors and the CRISPR/dCas9 in regulation of gene expression by targeting enhancers-
dc.typeArticle-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1093/nar/gku836-
dc.identifier.pmid25223790-
dc.identifier.scopuseid_2-s2.0-84964313405-
dc.identifier.volume42-
dc.identifier.issue20-
dc.identifier.spagenull-
dc.identifier.epagenull-
dc.identifier.eissn1362-4962-
dc.identifier.isiWOS:000347693200003-
dc.identifier.issnl0305-1048-

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