Transcriptional activators of human genes with programmable DNA-specificity.

Transcriptional activators of human genes with programmable DNA-specificity.
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DOI:
10.1371/journal.pone.0019509
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发表时间:
2011
期刊:
影响因子:
3.7
通讯作者:
Boch J
Boch J
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Geissler R;Scholze H;Hahn S;Streubel J;Bonas U;Behrens SE;Boch J

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TAL(转录激活剂)效应被黄虫细菌易位到植物细胞中,它们激活了靶基因的转录。连续的DNA序列和一对相邻的高变量氨基酸保留每个重复的重新分组。具有可预测的DNA识别特异性的蛋白质。 TAL技术”。以及内源性基因。 。
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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