Cong, L., et al. Nat. Comm. 3, 968 (2012).

The DNA binding domains of transcription activator–like effector (TALE) proteins from Xanthomonas are very promising for precise genomic targeting of various enzymatic activities. TALE DNA-binding domains consist of multiple 34-amino-acid repeats, each binding to a single nucleotide. Binding specificity is determined by amino acids 12 and 13, called the repeat variable diresidue (RVD), within each repeat. The TALE toolbox is still being developed. Cong et al. conducted a systematic transcription-activation screen to identify an RVD, Asn-His, that recognizes guanine in the target DNA with higher specificity and activity than currently used RVDs. In a separate screen of six transcription repressor domains from multiple species, they identified the mammalian SID domain as an effective repressor of endogenous gene expression when fused to a TALE.

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