Nucleosome-depleted regions in cell-cycle-regulated promoters ensure reliable gene expression in every cell cycle.
Nucleosome-depleted regions in cell-cycle-regulated promoters ensure reliable gene expression in every cell cycle.
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DOI：
10.1016/j.devcel.2010.02.007
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发表时间：
2010-04-20
影响因子：
11.8
通讯作者：
Cross, Frederick R.
中科院分区：
文献类型：
--
作者：
Bai, Lu;Charvin, Gilles;Siggia, Eric D.;Cross, Frederick R.
真核生物中的许多启动子具有含有转录因子结合位点（TFBS）的核小体耗尽区（NDR）。然而，NDR的功能意义并没有得到很好的理解。在这里，我们研究NDR功能在两个细胞周期调控的启动子，CLN 2 PR和HOPR，通过改变核小体覆盖的结合位点的激活剂SBF（SCBs）和探测相应的转录活性在单个细胞中使用延时显微镜。核小体包埋的SCB不显著改变峰值表达水平。相反，它们在单个细胞周期中诱导双峰，“开/关”激活，这显示了来自母亲周期的短期记忆或表观遗传。与此形成鲜明对比的是，位于NDR中的相同SCB导致高度可靠的激活，每个细胞周期一次。我们进一步证明了核小体SCBs诱导的Cln 2 p表达的高变异性降低了细胞适应性。因此，我们认为NDR限制基因表达随机性的功能促进了启动子NDR的普遍性和保守性。
Many promoters in eukaryotes have nucleosome depleted regions (NDR) containing transcription factor binding sites (TFBS). However, the functional significance of NDR 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 SBF (SCBs) and probing the corresponding transcriptional activity in individual cells using 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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影响因子：
9.8
作者：
Brickner DG;Cajigas I;Fondufe-Mittendorf Y;Ahmed S;Lee PC;Widom J;Brickner JH
通讯作者：
Brickner JH
影响因子：
5.3
作者：
CROSS, FR;HOEK, M;TINKELENBERG, AH
通讯作者：
TINKELENBERG, AH
影响因子：
16
作者：
Blake, William J.;Balazsi, Gbor;Collins, James J.
通讯作者：
Collins, James J.
影响因子：
4.8
作者：
Abbott, DW;Ivanova, VS;Ausió, J
通讯作者：
Ausió, J
影响因子：
5.3
作者：
Burns, LG;Peterson, CL
通讯作者：
Peterson, CL