TY - JOUR
T1 - Nucleosome-Depleted Regions in Cell-Cycle-Regulated Promoters Ensure Reliable Gene Expression in Every Cell Cycle
AU - Bai, Lu
AU - Charvin, Gilles
AU - Siggia, Eric D.
AU - Cross, Frederick R.
N1 - Funding Information:
The authors acknowledge Jon Widom and Irene Moore for advice on the MNase assay; Hisao Moriya for the pTOW-SWI4 plasmid; Craig Peterson for CY337 and CY407 strain; Lea Schroeder and Ying Lu for help with strain construction, and all the members of the F. Cross laboratory for insightful comments. This work was supported by the National Institutes of Health (E.D.S. and F.R.C.), the Damon Runyon Cancer Research Fellowship (L.B.), Human Frontier Science Program Organization (G.C.), and the National Science Foundation (E.D.S.).
PY - 2010/4
Y1 - 2010/4
N2 - 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:
AB - 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:
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U2 - 10.1016/j.devcel.2010.02.007
DO - 10.1016/j.devcel.2010.02.007
M3 - Article
C2 - 20412770
AN - SCOPUS:77951902484
VL - 18
SP - 544
EP - 555
JO - Developmental Cell
JF - Developmental Cell
SN - 1534-5807
IS - 4
ER -