Cell growth and gene expression, two essential elements of all living systems, have long been the focus of biophysical interrogation. Advances in experimental single-cell methods have invigorated theoretical studies into these processes. However, until recently there was little dialogue between the two areas of study. In particular, most theoretical models for gene regulation assumed gene activity to be oblivious to the progression of the cell cycle between birth and division. But in fact there are numerous ways in which the periodic character of all cellular observables can modulate gene expression. The molecular factors required for transcription and translation [ribonucleic acid (RNA) polymerase, transcription factors, and ribosomes] increase in number during the cell cycle but are also diluted due to the continuous increase in cell volume. The replication of the genome changes the dosage of those same cellular players but also provides competing targets for regulatory binding. Finally, cell division reduces their number again, and so forth. Stochasticity is inherent to all of these biological processes, manifested in fluctuations in the synthesis and degradation of new cellular components as well as the random partitioning of molecules at each cell division event. The notion of gene expression as stationary is thus difficult to justify. In this review, the emerging paradigm of cell-cycle coupled gene expression is surveyed, with an emphasis on the global expression patterns rather than gene-specific regulation. Recent experimental reports where cell growth and gene expression were simultaneously measured in individual cells are discussed, providing first glimpses into the coupling between the two and prompting several questions. How do the levels of gene expression products (messenger RNA and protein) scale with the cell volume and cell-cycle progression? What are the molecular origins of the observed scaling laws, and when do they break down to yield noncanonical behavior? What are the consequences of cell-cycle dependence for the heterogeneity (“noise”) in gene expression within a cell population? While the experimental findings differ among genes, organisms, and environmental conditions, several theoretical models have emerged that attempt to reconcile these differences and form a unifying framework for understanding gene expression in growing cells.

中文翻译：

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专题讨论会：生长细胞中的基因表达：生物物理入门


细胞生长和基因表达是所有生命系统的两个基本要素，长期以来一直是生物物理学研究的重点。实验性单细胞方法的进步为这些过程的理论研究注入了活力。然而，直到最近，这两个研究领域之间几乎没有对话。特别是，大多数基因调控理论模型都假设基因活动对细胞周期从出生到分裂之间的进展视而不见。但事实上，所有细胞可观察对象的周期性特征可以通过多种方式调节基因表达。转录和翻译所需的分子因子 [核糖核酸 （RNA） 聚合酶、转录因子和核糖体] 在细胞周期中数量增加，但由于细胞体积的持续增加，也会被稀释。基因组的复制改变了这些相同细胞参与者的剂量，但也为调节结合提供了竞争性靶标。最后，细胞分裂再次减少它们的数量，依此类推。随机性是所有这些生物过程所固有的，表现为新细胞成分的合成和降解的波动，以及每次细胞分裂事件中分子的随机分配。因此，基因表达是平稳的概念很难证明。在这篇综述中，调查了细胞周期偶联基因表达的新兴范式，重点是全局表达模式而不是基因特异性调控。讨论了最近在单个细胞中同时测量细胞生长和基因表达的实验报告，初步了解了两者之间的耦合并引发了几个问题。 基因表达产物（信使 RNA 和蛋白质）的水平如何随细胞体积和细胞周期进程而变化？观察到的缩放定律的分子起源是什么，它们何时分解产生非经典行为？细胞周期依赖性对细胞群内基因表达的异质性（“噪音”）有什么影响？虽然实验结果因基因、生物体和环境条件而异，但已经出现了几种理论模型，试图调和这些差异并形成一个统一的框架来理解生长细胞中的基因表达。