Nucleosome-Depleted Regions in Cell-Cycle-Regulated Promoters Ensure Reliable Gene Expression in Every Cell Cycle

SummaryMany promoters in eukaryotes have nucleosome-depleted regions (NDRs) containing transcription factor binding sites. However, the functional significance of NDRs is not well understood. Here, we examine NDR function in two cell cycle-regulated promoters, CLN2pr and HOpr, by varying nucleosomal coverage of the binding sites of their activator, Swi4/Swi6 cell-cycle box (SCB)-binding factor (SBF), and probing the corresponding transcriptional activity in individual cells with time-lapse microscopy. Nucleosome-embedded SCBs do not significantly alter peak expression levels. Instead, they induce bimodal, “on/off” activation in individual cell cycles, which displays short-term memory, or epigenetic inheritance, from the mother cycle. In striking contrast, the same SCBs localized in NDR lead to highly reliable activation, once in every cell cycle. We further demonstrate that the high variability in Cln2p expression induced by the nucleosomal SCBs reduces cell fitness. Therefore, we propose that the NDR function in limiting stochasticity in gene expression promotes the ubiquity and conservation of promoter NDR.PaperClip To listen to this audio, enable JavaScript on your browser. However, you can download and play the audio by clicking on the icon belowHelp with MP3 filesOptionsDownload audio (3596 K)

► Many transcription factors bind target motifs in nucleosome-depleted regions (NDR)
► On a cell-cycle-regulated promoter, NDR ensures reliable, once-per-cycle activation
► In contrast, nucleosomal factor binding sites induce bimodal, “on/off” expression
► NDR limits stochasticity in gene expression and ensures robust cell cycle control