Liu Ping, Song Ruijie, Elison Gregory L, Peng Weilin, Acar Murat
Department of Molecular Cellular and Developmental Biology, Yale University, 219 Prospect Street, New Haven, CT, 06511, USA.
Systems Biology Institute, Yale University, 850 West Campus Drive, West Haven, CT, 06516, USA.
Nat Commun. 2017 Sep 25;8(1):680. doi: 10.1038/s41467-017-00752-9.
Noise-induced heterogeneity in gene expression is an inherent reality for cells. However, it is not well understood how noise strength changes for a single gene while the host cell is aging. Using a state-of-the-art microfluidic platform, we measure noise dynamics in aging yeast cells by tracking the generation-specific activity of the canonical GAL1 promoter. We observe noise reduction during normal aging of a cell, followed by a short catastrophe phase in which noise increased. We hypothesize that aging-associated increases in chromatin state transitions are behind the observed noise reduction and a stochastic model provides quantitative support to the proposed mechanism. Noise trends measured from strains with altered GAL1 promoter dynamics (constitutively active, synthetic with nucleosome-disfavoring sequences, and in the absence of RPD3, a global remodeling regulator) lend further support to our hypothesis. Observing similar noise dynamics from a different promoter (HHF2) provides support to the generality of our findings.Gene expression is a noisy process, but it is not known how noise in gene expression changes during the aging of single cells. Here the authors show that noise decreases during normal aging, and provide support for aging-associated increases in chromatin state transitions governing noise reduction.
噪声诱导的基因表达异质性是细胞的固有现实。然而，对于单个基因在宿主细胞衰老过程中噪声强度如何变化，人们还了解得不够清楚。利用最先进的微流控平台，我们通过追踪典型GAL1启动子的代际特异性活性来测量衰老酵母细胞中的噪声动态。我们观察到细胞正常衰老过程中噪声降低，随后是一个短暂的突变阶段，在此期间噪声增加。我们推测，观察到的噪声降低背后是与衰老相关的染色质状态转变增加，并且一个随机模型为所提出的机制提供了定量支持。从具有改变的GAL1启动子动态（组成型激活、与不利于核小体的序列合成以及在缺乏全局重塑调节因子RPD3的情况下）的菌株中测量到的噪声趋势进一步支持了我们的假设。从不同启动子（HHF2）观察到类似的噪声动态为我们研究结果的普遍性提供了支持。基因表达是一个有噪声的过程，但尚不清楚基因表达中的噪声在单细胞衰老过程中如何变化。在这里，作者表明在正常衰老过程中噪声会降低，并为与衰老相关的染色质状态转变增加控制噪声降低提供了支持。
