Transcriptional activators of human genes with programmable DNA-specificity.

TAL (transcription activator-like) effectors are translocated by Xanthomonas bacteria into plant cells where they activate transcription of target genes. DNA target sequence recognition occurs in a unique mode involving a central domain of tandem repeats. Each repeat recognizes a single base pair in...

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Autores principales: René Geissler, Heidi Scholze, Simone Hahn, Jana Streubel, Ulla Bonas, Sven-Erik Behrens, Jens Boch
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Publicado: Public Library of Science (PLoS) 2011
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Acceso en línea:https://doaj.org/article/7ff6afeaea36486f9008c321137fc741
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spelling oai:doaj.org-article:7ff6afeaea36486f9008c321137fc7412021-11-18T06:53:37ZTranscriptional activators of human genes with programmable DNA-specificity.1932-620310.1371/journal.pone.0019509https://doaj.org/article/7ff6afeaea36486f9008c321137fc7412011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21625585/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203TAL (transcription activator-like) effectors are translocated by Xanthomonas bacteria into plant cells where they activate transcription of target genes. DNA target sequence recognition occurs in a unique mode involving a central domain of tandem repeats. Each repeat recognizes a single base pair in a contiguous DNA sequence and a pair of adjacent hypervariable amino acid residues per repeat specifies which base is bound. Rearranging the repeats allows the design of novel TAL proteins with predictable DNA-recognition specificities. TAL protein-based transcriptional activation in plant cells is mediated by a C-terminal activation domain (AD). Here, we created synthetic TAL proteins with designed repeat compositions using a novel modular cloning strategy termed "Golden TAL Technology". Newly programmed TAL proteins were not only functional in plant cells, but also in human cells and activated targeted expression of exogenous as well as endogenous genes. Transcriptional activation in different human cell lines was markedly improved by replacing the TAL-AD with the VP16-AD of herpes simplex virus. The creation of TAL proteins with potentially any desired DNA-recognition specificity allows their versatile use in biotechnology.René GeisslerHeidi ScholzeSimone HahnJana StreubelUlla BonasSven-Erik BehrensJens BochPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 5, p e19509 (2011)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
René Geissler
Heidi Scholze
Simone Hahn
Jana Streubel
Ulla Bonas
Sven-Erik Behrens
Jens Boch
Transcriptional activators of human genes with programmable DNA-specificity.
description TAL (transcription activator-like) effectors are translocated by Xanthomonas bacteria into plant cells where they activate transcription of target genes. DNA target sequence recognition occurs in a unique mode involving a central domain of tandem repeats. Each repeat recognizes a single base pair in a contiguous DNA sequence and a pair of adjacent hypervariable amino acid residues per repeat specifies which base is bound. Rearranging the repeats allows the design of novel TAL proteins with predictable DNA-recognition specificities. TAL protein-based transcriptional activation in plant cells is mediated by a C-terminal activation domain (AD). Here, we created synthetic TAL proteins with designed repeat compositions using a novel modular cloning strategy termed "Golden TAL Technology". Newly programmed TAL proteins were not only functional in plant cells, but also in human cells and activated targeted expression of exogenous as well as endogenous genes. Transcriptional activation in different human cell lines was markedly improved by replacing the TAL-AD with the VP16-AD of herpes simplex virus. The creation of TAL proteins with potentially any desired DNA-recognition specificity allows their versatile use in biotechnology.
format article
author René Geissler
Heidi Scholze
Simone Hahn
Jana Streubel
Ulla Bonas
Sven-Erik Behrens
Jens Boch
author_facet René Geissler
Heidi Scholze
Simone Hahn
Jana Streubel
Ulla Bonas
Sven-Erik Behrens
Jens Boch
author_sort René Geissler
title Transcriptional activators of human genes with programmable DNA-specificity.
title_short Transcriptional activators of human genes with programmable DNA-specificity.
title_full Transcriptional activators of human genes with programmable DNA-specificity.
title_fullStr Transcriptional activators of human genes with programmable DNA-specificity.
title_full_unstemmed Transcriptional activators of human genes with programmable DNA-specificity.
title_sort transcriptional activators of human genes with programmable dna-specificity.
publisher Public Library of Science (PLoS)
publishDate 2011
url https://doaj.org/article/7ff6afeaea36486f9008c321137fc741
work_keys_str_mv AT renegeissler transcriptionalactivatorsofhumangeneswithprogrammablednaspecificity
AT heidischolze transcriptionalactivatorsofhumangeneswithprogrammablednaspecificity
AT simonehahn transcriptionalactivatorsofhumangeneswithprogrammablednaspecificity
AT janastreubel transcriptionalactivatorsofhumangeneswithprogrammablednaspecificity
AT ullabonas transcriptionalactivatorsofhumangeneswithprogrammablednaspecificity
AT svenerikbehrens transcriptionalactivatorsofhumangeneswithprogrammablednaspecificity
AT jensboch transcriptionalactivatorsofhumangeneswithprogrammablednaspecificity
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