Several natural transcription factors turn genes on by enticing RNA polymerase and its protein entourage to specific locations in the genome, thereby initiating the transcription of genes into messenger RNA. Gene-activating transcription factors also set the stage for RNA polymerase by unwinding DNA from where it is tightly packed around histone proteins and by enlisting enzymes to remove chemical marks on the genome that end up blocking the polymerase's progress. Transcription factors can also turn off genes by physically obstructing transcription machinery from assembling on DNA or by jamming RNA polymerase in midtranscription. Precise control of gene expression with synthetic transcription factors also would serve as a useful tool for understanding and manipulating the activity of cells. Researchers are thereby learning to turn gene transcription on and off with transcription factors as they play a key role as protectors.