Regulation of endogenous human gene expression by ligand-inducible TALE transcription factors

Andrew C. Mercer, Thomas Gaj, Shannon J. Sirk, Brian M. Lamb, Carlos F. Barbas

Research output: Contribution to journalArticle

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. (Figure Presented).

Original languageEnglish (US)
Pages (from-to)723-730
Number of pages8
JournalACS synthetic biology
Volume3
Issue number10
DOIs
StatePublished - Oct 17 2014

Keywords

  • Gene regulation
  • Inducible gene expression
  • Steroid hormone receptor
  • TALE
  • Transcription factor

ASJC Scopus subject areas

  • Biomedical Engineering
  • Biochemistry, Genetics and Molecular Biology (miscellaneous)

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