New tricks of TALEs: Discovery of a new principle of gene regulation by molecular displacement | 11/26/2018 | Staff
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Transcription activator-like effector (TALE) proteins can be designed to bind to almost any selected DNA. Researchers now report that a TALE can displace another TALE protein from DNA in a highly polarized way – it can displace a TALE protein binding to DNA adjacent to its right but not its left side. This unusual property of TALEs has been used to increase the precision of gene expression regulation, to design logic circuits in mammalian cells, and to prevent CRISPR cleavage at non-desired DNA sites.

Properties of cells are defined by a DNA program that is hardwired into the genome. Gene activity is defined by proteins that bind to the DNA in close proximity. Synthetic biology can manipulate gene activation by designed proteins, which can be targeted to bind selected DNA targets. Almost a decade ago, scientists deciphered DNA sequence recognition for a group of proteins called TALEs (short for transcription activator-like effectors), which were first found in bacteria that infect plants. Understanding of this code enabled researchers to design TALE proteins that bind to practically any selected DNA sequence. The addition of a small protein appendix that causes the genes to become active or inactive can be added to any TALE protein, which enables activation or inactivation of any gene, making them very useful for medical therapy and biotechnology.

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TALES have been somewhat overshadowed by CRISPR technology, which can do the same things as TALEs, but is easier to work with. Lebar et al. now show that TALEs are able to perform some additional tricks that may bring them back into the spotlight. The Slovenian researchers discovered that when two TALEs bind next to each other, the one bound on the left is able to dislodge the TALE bound to DNA on its right, but not vice versa.

Project leader Roman Jerala, head...
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