Synergistic and tunable human gene activation by combinations of synthetic transcription factors.

Perez-Pinera P, Ousterout DG, Brunger JM, Farin AM, Glass KA, Guilak F, Crawford GE, Hartemink AJ, Gersbach CA
Nat Methods. 2013 10 (3): 239-42

PMID: 23377379 · PMCID: PMC3719416 · DOI:10.1038/nmeth.2361

Mammalian genes are regulated by the cooperative and synergistic actions of many transcription factors. In this study we recapitulate this complex regulation in human cells by targeting endogenous gene promoters, including regions of closed chromatin upstream of silenced genes, with combinations of engineered transcription activator-like effectors (TALEs). These combinations of TALE transcription factors induced substantial gene activation and allowed tuning of gene expression levels that will broadly enable synthetic biology, gene therapy and biotechnology.

MeSH Terms (18)

Binding Sites Blotting, Western Carcinoembryonic Antigen Enzyme-Linked Immunosorbent Assay Genetic Engineering GPI-Linked Proteins HEK293 Cells Humans Kallikreins Luciferases Plasmids Promoter Regions, Genetic Prostate-Specific Antigen Real-Time Polymerase Chain Reaction Receptor, ErbB-2 Transcriptional Activation Transcription Factors Transfection

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