Anti-Transcription Factor RNA Aptamers as Potential Therapeutics
Although the majority of the transcription factors that were initially characterized had a stimulatory effect on gene expression, it is now clear that transcription factors that inhibit gene transcription are at least as important in regulating a wide variety of processes, including development. These factors can act either by interfering with the action of a positively acting factor (indirect repression) or by directly interfering with transcription by interacting with the basal transcriptional complex of RNA polymerase and associated factors (direct repression). Indirect repression often operates by the negative factor preventing the positively acting factor binding to DNA. This can involve reorganization of chromatin structure, blockage of the binding site in the DNA by binding of the inhibitory factor or formation of a non-DNA binding protein-protein complex. Indirect repression can also occur via quenching of the activity of a positive factor that remains bound to DNA. Direct repression can be produced by factors that interact with the basal transcriptional complex to reduce its activity or stability. This can be achieved either by factors that interact with the complex following binding to DNA or by those which bind directly to it. Factors that act by each of these means, and their mechanisms of action, are discussed.