Mercer Andrew C, Gaj Thomas, Sirk Shannon J, Lamb Brian M, Barbas Carlos F
The Skaggs Institute for Chemical Biology and the Departments of Chemistry and Cell and Molecular Biology, The Scripps Research Institute , La Jolla, California 92037, United States.
ACS Synth Biol. 2014 Oct 17;3(10):723-30. doi: 10.1021/sb400114p. Epub 2013 Nov 22.
The construction of increasingly sophisticated synthetic biological circuits is dependent on the development of extensible tools capable of providing specific control of gene expression in eukaryotic cells. Here, we describe a new class of synthetic transcription factors that activate gene expression in response to extracellular chemical stimuli. These inducible activators consist of customizable transcription activator-like effector (TALE) proteins combined with steroid hormone receptor ligand-binding domains. We demonstrate that these ligand-responsive TALE transcription factors allow for tunable and conditional control of gene activation and can be used to regulate the expression of endogenous genes in human cells. Since TALEs can be designed to recognize any contiguous DNA sequence, the conditional gene regulatory system described herein will enable the design of advanced synthetic gene networks.
构建日益复杂的合成生物电路依赖于可扩展工具的开发，这些工具能够对真核细胞中的基因表达进行特定控制。在此，我们描述了一类新型的合成转录因子，它们可响应细胞外化学刺激激活基因表达。这些诱导型激活剂由可定制的转录激活因子样效应物（TALE）蛋白与类固醇激素受体配体结合域组成。我们证明，这些配体响应型TALE转录因子能够对基因激活进行可调谐和条件性控制，并可用于调节人类细胞中内源基因的表达。由于TALE可被设计用于识别任何连续的DNA序列，本文所述的条件性基因调控系统将有助于设计先进的合成基因网络。
