Figure 1. Example of a natural transcription factor up-regulating gene expression. 1. The transcription factors (labeled activator proteins) bind to their specific DNA sequence (labeled enhancers). 2. The transcription factors recruit other proteins and transcription factors to form a protein complex which binds to the gene promoter. 3. After the activating protein complex binds to the promoter, RNA polymerase easily binds and starts transcribing the target gene. 4. and 5. are additional scenarios where in 4. an insulator/inhibitor can bind to the DNA preventing activation for transcription and in 5. methylation can prevent the insulator from binding.
Artificial transcription factors (ATFs) are engineered individual or multi molecule transcription factors that either activate or repress gene transcription (biology).[1]
ATFs often contain two main components linked together, a DNA-binding domain and a regulatory domain, also known as an effector domain or modulatory domain.[1] The DNA-binding domain targets a specific DNA sequence with high affinity, and the regulatory domain is responsible for activating or repressing the bound gene.[1] The ATF can directly regulate gene expression, can recruit proteins and other transcription factors to initiate transcription, or recruit proteins and other transcription factors to compact the DNA which inhibits RNA polymerase from binding and transcribing the DNA; an example of transcription factors up-regulating gene expression is displayed in figure 1 on the left.[1][2] Because ATFs are composed of two separable components, the DNA-binding domain and the regulatory domain, the two domains are interchangeable, permitting the design of new ATFs from existing natural transcription factors.[1]
Some applications of ATFs include reprogramming cell state, cancer treatment, and a plausible treatment for Angelman Syndrome.[2][3][4]
^ abcdeAnsari, Aseem Z; Mapp, Anna K (2002-12-01). "Modular design of artificial transcription factors". Current Opinion in Chemical Biology. 6 (6): 765–772. doi:10.1016/S1367-5931(02)00377-0. ISSN 1367-5931. PMID 12470729.
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