Nucleosome-depleted regions in cell-cycle-regulated promoters ensure reliable gene expression in every cell cycle.
Many 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:
Bai
Lu
L
Center for Studies in Physics and Biology, The Rockefeller University, New York, NY 10065, USA. lbai01@rockefeller.edu
Charvin
Gilles
G
Siggia
Eric D
ED
Cross
Frederick R
FR
D001665:Binding Sites; D002453:Cell Cycle; D016213:Cyclins / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D044127:Epigenesis, Genetic; D015966:Gene Expression Regulation, Fungal; D007700:Kinetics; D008856:Microscopy, Fluorescence / Q000379:methods; D008954:Models, Biological; D008957:Models, Genetic; D009707:Nucleosomes / Q000737:chemistry / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D013269:Stochastic Processes; D014157:Transcription Factors / Q000378:metabolism
C082721:CLN2 protein, S cerevisiae; D016213:Cyclins; D004268:DNA-Binding Proteins; D009707:Nucleosomes; C062214:SWI4 protein, S cerevisiae; C075111:SWI6 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors