Regulatory Mechanism and Functional Significance of Divergent Gene Pairs
Divergent gene pairs (DGPs) are abundant in eukaryotic genomes. In yeast, about 50% of the whole genome is organized in DGPs. Despite the fact that the two genes in a DGP are very close together and potentially share the same cis regulatory elements, most DGPs in the yeast genome are not co-regulated. We investigated how the two genes in a DGP can be “decoupled” in their regulation. Our bioinformatics analyses showed that co- versus differential regulation cannot be explained by several genetic features, including the promoter length, binding site orientation, TATA elements, nucleosome distribution, or presence of non-coding RNAs. Instead, for a differentially regulated DGP, PFK26-MOB1, we found that the decoupling is mainly achieved through two DNA-binding factors, Tbf1 and Mcm1. Similar to “enhancer-blocking insulators” in higher eukaryotes, these factors shield the proximal promoter from the action of more distant transcription regulators. Interestingly, this blockage mechanism is not 100% robust – the regulatory signal of PFK26 can occasionally “leak” to MOB1, increasing the cell-to-cell variability (noise) of MOB1 expression.