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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Public Library of Science (PLoS)
2011
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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) |
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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 |
_version_ |
1718424239010217984 |