title: Regulation of endogenous human gene expression by ligand-inducible TALE transcription factors.
abstract: 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.
authors.affiliation: 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.
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Mercer
authors.forename: Thomas
authors.initials: T
authors.lastname: Gaj
authors.forename: Shannon J
authors.initials: SJ
authors.lastname: Sirk
authors.forename: Brian M
authors.initials: BM
authors.lastname: Lamb
authors.forename: Carlos F
authors.initials: CF
authors.lastname: Barbas
mesh_terms: D001483:Base Sequence; D004247:DNA / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D008024:Ligands; D015202:Protein Engineering; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism; D011980:Receptors, Progesterone / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D058615:Synthetic Biology; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*
chemical_list: D008024:Ligands; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D011993:Recombinant Fusion Proteins; D015534:Trans-Activators; D004247:DNA
keywords: TALE; gene regulation; inducible gene expression; steroid hormone receptor; transcription factor