Université de Lyon, Université Lyon 1, Centre de Génétique et de Physiologie Moléculaire et Cellulaire (CGPhiMC), CNRS UMR5534, F-69622 Lyon, France.
Prog Biophys Mol Biol. 2012 Sep;110(1):44-53. doi: 10.1016/j.pbiomolbio.2012.04.010. Epub 2012 May 16.
For decades, most of molecular biology was driven by the "central dogma" in which the phenotype is defined by the genotype following a fully deterministic point of view. However, during the last 10 years, a wealth of studies has demonstrated that a given genotype can generate multiple phenotypes in identical environmental conditions, mainly because of the inherently probabilistic nature of the transcription process. It has also been shown that cells can tune this variability at the molecular level. Although previously described as a useless "noise", stochastic gene expression has now been shown by many authors to be an essential part of diverse biological processes. Chromatin dynamics having a central role in higher eukaryotes, we decided to investigate its involvement in the generation and control of stochasticity in gene expression (SGE). Our experiments reveal that the chromatin environment of a gene plays an important role in regulating SGE. Indeed, we find that histone acetylation and DNA methylation significantly affect SGE, suggesting that cells are able to adjust the variability of the expression of their genes through modification of chromatin marks. Given that the alteration of chromatin marks is itself subject to the expression of chromatin modifiers, our results shed light on a complex circular causality with on the one hand, the effect of gene expression on chromatin and on the other hand, the influence of the local chromatin environment of a gene on the dynamics of its expression.
几十年来，大多数分子生物学都是由“中心法则”驱动的，该法则从完全确定的角度定义表型由基因型决定。然而，在过去的 10 年中，大量的研究表明，在相同的环境条件下，给定的基因型可以产生多种表型，主要是因为转录过程本质上是概率性的。还表明，细胞可以在分子水平上调节这种可变性。尽管先前被描述为无用的“噪声”，但随机基因表达现在已被许多作者证明是多种生物过程的重要组成部分。染色质动力学在真核生物中起着核心作用，我们决定研究其在基因表达的随机性（SGE）的产生和控制中的作用。我们的实验表明，基因的染色质环境在调节 SGE 方面起着重要作用。事实上，我们发现组蛋白乙酰化和 DNA 甲基化显著影响 SGE，这表明细胞能够通过修饰染色质标记来调整其基因表达的可变性。鉴于染色质标记的改变本身受到染色质修饰物的表达的影响，我们的结果揭示了一种复杂的循环因果关系，一方面是基因表达对染色质的影响，另一方面是基因局部染色质环境对其表达动态的影响。
