PT - JOURNAL ARTICLE AU - Orlando de Lange AU - Niklas Schandry AU - Markus Wunderlich AU - Kenneth Berendzen AU - Thomas Lahaye TI - Tunable synthetic transcription factors assembled from TALE-like repeat elements AID - 10.1101/068908 DP - 2016 Jan 01 TA - bioRxiv PG - 068908 4099 - http://biorxiv.org/content/early/2016/08/11/068908.short 4100 - http://biorxiv.org/content/early/2016/08/11/068908.full AB - A protein-DNA interface can be engineered in ways that an RNA-DNA interface cannot. Programmable TAL effector derived proteins bind DNA with a series of repeats. Each repeat binds a single DNA base. Repeats can be treated as modules, with a pair of residues in the center defining the target base. A set of 31-33 residues flanking the base specifying residues affect other DNA binding parameters. Efforts at engineering TAL effector DNA binding repeats have till now focused on the base specifying residues only. Here we show that natural repeat sequence diversity can be used to alter DNA binding strength. We generated sets of chimeric repeat arrays through a random assembly approach. These sequence diverse repeat proteins activate or repress promoters with a range of activities. Our design leaves the choice of base binding residues for each repeat open. This allows users to tune binding strength without altering sequence preference.