Transcriptional activators of human genes with programmable DNA-specificity

Publikation: Beitrag in FachzeitschriftArtikelForschungPeer-Review

Autoren

  • René Geißler
  • Heidi Scholze
  • Simone Hahn
  • Jana Streubel
  • Ulla Bonas
  • Sven Erik Behrens
  • Jens Boch

Externe Organisationen

  • Martin-Luther-Universität Halle-Wittenberg
Forschungs-netzwerk anzeigen

Details

OriginalspracheEnglisch
Aufsatznummere19509
FachzeitschriftPLoS ONE
Jahrgang6
Ausgabenummer5
PublikationsstatusVeröffentlicht - 19 Mai 2011
Extern publiziertJa

Abstract

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.

ASJC Scopus Sachgebiete

Zitieren

Transcriptional activators of human genes with programmable DNA-specificity. / Geißler, René; Scholze, Heidi; Hahn, Simone et al.
in: PLoS ONE, Jahrgang 6, Nr. 5, e19509, 19.05.2011.

Publikation: Beitrag in FachzeitschriftArtikelForschungPeer-Review

Geißler, R, Scholze, H, Hahn, S, Streubel, J, Bonas, U, Behrens, SE & Boch, J 2011, 'Transcriptional activators of human genes with programmable DNA-specificity', PLoS ONE, Jg. 6, Nr. 5, e19509. https://doi.org/10.1371/journal.pone.0019509
Geißler, R., Scholze, H., Hahn, S., Streubel, J., Bonas, U., Behrens, S. E., & Boch, J. (2011). Transcriptional activators of human genes with programmable DNA-specificity. PLoS ONE, 6(5), Artikel e19509. https://doi.org/10.1371/journal.pone.0019509
Geißler R, Scholze H, Hahn S, Streubel J, Bonas U, Behrens SE et al. Transcriptional activators of human genes with programmable DNA-specificity. PLoS ONE. 2011 Mai 19;6(5):e19509. doi: 10.1371/journal.pone.0019509
Geißler, René ; Scholze, Heidi ; Hahn, Simone et al. / Transcriptional activators of human genes with programmable DNA-specificity. in: PLoS ONE. 2011 ; Jahrgang 6, Nr. 5.
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AU - Geißler, René

AU - Scholze, Heidi

AU - Hahn, Simone

AU - Streubel, Jana

AU - Bonas, Ulla

AU - Behrens, Sven Erik

AU - Boch, Jens

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N2 - 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.

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