Nucleosome Depleted Region In Promoter Improves Robustness In Gene Expression

Abstract

Nucleosomes assembled onto promoters are critical for eukaryotic transcription regulation. Recent genome wide mapping of nucleosome positioning in Saccharomyces cerevisiae revealed that many promoters have nucleosome depleted region (NDR) that contains the transcription factor (TF) binding sites (TFBS), presumably to provide access for the factors. However, the necessity and advantage of this configuration is not well understood. We perturbed the relative position between TFBS and nucleosomes on two G1/S cell-cycle regulated promoters, and used time-lapse fluorescence microscopy to probe their transcriptional activity in individual cells through multiple cell cycles. We find that although localization of TFBSs to NDR is not required for transcription activation, it significantly reduces variability in expression between cell cycles. TFBSs localized to NDR activate transcription in every cell cycle with high reliability. In contrast, when the same TFBSs are located within positioned nucleosomes, activation was bimodal: nearly fully active in some cell cycles, and essentially undetectable in others. Interestingly, this “on/off” transcription pattern displays short-term “memory”, or epigenic inheritance, from the previous mother cell cycle. Furthermore, the probability of “on/off” cycles could be affected by varying the TF concentration and nucleosome acetylation level. Our results have significant implications for the function and evolution of NDR, and for the relationship between the chromatin structure on promoters and the reliability of gene expression.