期刊
DEVELOPMENTAL CELL
卷 18, 期 4, 页码 544-555出版社
CELL PRESS
DOI: 10.1016/j.devcel.2010.02.007
关键词
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资金
- National Institutes of Health
- Damon Runyon Cancer Research Fellowship
- Human Frontier Science Program Organization
- National Science Foundation
- Direct For Mathematical & Physical Scien
- Division Of Materials Research [0804721] Funding Source: National Science Foundation
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.
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