Controlling gene expression using synthetic ligands.
Chemical inducers of dimerization (dimerizers) are a new class of reagents used for controlling protein-protein interactions. Use of a small-molecule, cell-permeable dimerizer to control the interaction of a transcription activation domain and a DNA-binding domain allows the level of expression of a target gene to be regulated by the concentration of dimerizer. The modular design of components has facilitated the development of multiple systems that can be used to readily generate cell lines in which basal expression of the target gene is low and induced to high levels by a nontoxic dimerizer. The development and use of one such system to control the expression of a gene in cultured cells are described.
Rivera
V M
VM
ARIAD Gene Therapeutics, Cambridge, Massachusetts 02139, USA. vrivera@ariad.com
D002460:Cell Line; D002934:Cinnamates; D002999:Clone Cells / Q000187:drug effects / Q000378:metabolism; D003001:Cloning, Molecular / Q000379:methods; D019281:Dimerization; D005786:Gene Expression Regulation / Q000502:physiology*; D018390:Gene Targeting / Q000379:methods*; D005822:Genetic Vectors / Q000138:chemical synthesis / Q000235:genetics*; D006801:Humans; D006921:Hygromycin B / Q000031:analogs & derivatives / Q000494:pharmacology; D008024:Ligands; D010957:Plasmids / Q000138:chemical synthesis / Q000235:genetics; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics; D014162:Transfection
D002934:Cinnamates; D008024:Ligands; D014157:Transcription Factors; D006921:Hygromycin B; C026273:hygromycin A