Regulation of transcription factors via natural decoys in genomic DNA

Abstract

Eukaryotic genomic DNA contains numerous high-affinity sites for transcription factors. Only a small fraction of these sites directly regulates target genes. Other high-affinity sites can serve as naturally present decoys that sequester transcription factors. Such natural decoys in genomic DNA may provide novel regulatory mechanisms for transcription factors.

Keywords: decoy; regulatory elements; sequestration; target search; transcription factors.

Figure 1.

Natural decoys (NDs) for a transcription factor. (A) The recognition sequence and high-affinity quasi-specific sequences for Egr-1. (B) The influence of NDs on the target association kinetics of a transcription factor (TF). NDs preclude TFs from their targets. When all NDs are occupied by proteins, target association is drastically increased because the inhibitory effects of the NDs are eliminated. This phenomenon creates an on-off switch-like response.

Figure 2.

Potential mechanisms for the regulation of transcription factors via natural decoys (NDs). The accessibility of NDs may be modulated by other proteins, DNA methylation, and chromatin structures. When most NDs for a transcription factor become inaccessible, the transition from the “off” state to the “on” state (see Fig. 1B) may occur, which enhances the activity of the transcription factor.