Recent studies suggest that there are many nonfunctional transcription factor binding sites along a genome. Although these "decoy" sites compete with the promoter region for binding of transcription factors, they may also protect these proteins from degradation. We show that in the limit of perfect protection, where bound transcription factors are never degraded, the competitive effect of nonfunctional binding sites is completely canceled out by the stability gained from reduced degradation. We examine the response of an autoregulated gene to the total number of transcription factors to quantify the consequences of competition for transcription factors. We show that intuition about this system can be gained by mathematically constructing a single gene with effective parameters that reproduce the behavior of a gene with added decoy sites. In analogy to dressed particles in many-body systems we term this description a "quasi gene." We find that protective decoys buffer against noise by reducing correlations between transcription factors, specifically in the case of production of transcription factors in bursts. We show that the addition of protective decoy sites causes the level of gene expression to approach that predicted from deterministic mass action models. Finally, we show that protective decoy sites decrease the size of the region of parameter space that exhibits bistability.autoregulation | noise | stochastic gene expression | nonfunctional binding site

Pioneer transcription factors initiate cell-fate changes by binding to silent target genes. They are among the first factors to bind key regulatory sites and facilitate chromatin opening. Here, we identify an additional role for pioneer factors. In early Caenorhabditis elegans foregut development, the pioneer factor PHA-4/FoxA binds promoters and recruits RNA polymerase II (Pol II), often in a poised configuration in which Pol II accumulates near transcription start sites. At a later developmental stage, PHA-4 promotes chromatin opening. We found many more genes with poised RNA polymerase than had been observed previously in unstaged embryos, revealing that early embryos accumulate poised Pol II and that poising is dynamic. Our results suggest that Pol II recruitment, in addition to chromatin opening, is an important feature of PHA-4 pioneer factor activity.

Many transcription factors bind to DNA with a remarkable lack of specificity, so that regulatory binding sites compete with an enormous number of non-regulatory 'decoy' sites. For an autoregulated gene, we show decoy sites decrease noise in the number of unbound proteins to a Poisson limit that results from binding and unbinding. This noise buffering is optimized for a given protein concentration when decoys have a 1/2 probability of being occupied. Decoys linearly increase the time to approach steady state and exponentially increase the time to switch epigenetically between bistable states.