title: Synergistic and tunable human gene activation by combinations of synthetic transcription factors.
abstract: 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.
authors: Department of Biomedical Engineering, Duke University, Durham, North Carolina, USA.
authors: Pablo
authors: P
authors: Perez-Pinera
authors: David G
authors: DG
authors: Ousterout
authors: Jonathan M
authors: JM
authors: Brunger
authors: Alicia M
authors: AM
authors: Farin
authors: Katherine A
authors: KA
authors: Glass
authors: Farshid
authors: F
authors: Guilak
authors: Gregory E
authors: GE
authors: Crawford
authors: Alexander J
authors: AJ
authors: Hartemink
authors: Charles A
authors: CA
authors: Gersbach
mesh_terms: D001665:Binding Sites; D015153:Blotting, Western; D002272:Carcinoembryonic Antigen / Q000235:genetics*; D004797:Enzyme-Linked Immunosorbent Assay; D058851:GPI-Linked Proteins / Q000235:genetics; D005818:Genetic Engineering / Q000379:methods*; D057809:HEK293 Cells; D006801:Humans; D007610:Kallikreins / Q000235:genetics*; D008156:Luciferases / Q000235:genetics; D010957:Plasmids; D011401:Promoter Regions, Genetic; D017430:Prostate-Specific Antigen / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*; D015533:Transcriptional Activation; D014162:Transfection
chemical_list: D002272:Carcinoembryonic Antigen; D058851:GPI-Linked Proteins; D007610:Kallikreins; D008156:Luciferases; D017430:Prostate-Specific Antigen; D018719:Erb-b2 Receptor Tyrosine Kinases; D014157:Transcription Factors; C527875:CEACAM5 protein, human; C508053:ERBB2 protein, human; C549870:KLK3 protein, human
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