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PMID: 21625585 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Transcriptional activators of human genes with programmable DNA-specificity.

PloS one ·Vol. 6 ·No. 5 ·2011-00-00 ·Pages e19509

Geissler R, Scholze H, Hahn S, Streubel J, Bonas U, Behrens SE, Boch J

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.

MeSH Terms
Apoptosis Regulatory Proteins/genetics,metabolism Blotting, Western DNA/genetics,metabolism DNA-Binding Proteins/chemistry,genetics,metabolism HeLa Cells Herpes Simplex Virus Protein Vmw65/genetics Humans Interferon-alpha/genetics,metabolism Interferon-beta/genetics,metabolism Kidney/cytology,metabolism Luciferases/metabolism Proto-Oncogene Proteins/genetics,metabolism RNA, Messenger/genetics Repetitive Sequences, Amino Acid Reverse Transcriptase Polymerase Chain Reaction Transcriptional Activation Virulence Factors/genetics,metabolism
Chemicals
Apoptosis Regulatory Proteins BBC3 protein, human DNA-Binding Proteins Herpes Simplex Virus Protein Vmw65 Interferon-alpha Proto-Oncogene Proteins RNA, Messenger Virulence Factors Interferon-beta DNA Luciferases
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Geissler René
Section Microbial Biotechnology, Institute of Biochemistry and Biotechnology, Martin-Luther-University Halle-Wittenberg, Halle (Saale), Germany.
Scholze Heidi
Hahn Simone
Streubel Jana
Bonas Ulla
Behrens Sven-Erik
Boch Jens
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Article Info
Journal
PloS one
Abbr.
PLoS One
ISSN
1932-6203
DOI
10.1371/journal.pone.0019509
Published
2011-00-00
Epub
2011-00-19
Pages
e19509
Language
English
Region
United States
NLM ID
101285081
PMCID
PMC3098229
Subset
IM
External Links
PubMed source DOI: 10.1371/journal.pone.0019509 PMC Full Text View journal details
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