Epigenetic and conventional regulation is distributed among activators of FLO11 allowing tuning of population-level heterogeneity in its expression.
Epigenetic and conventional regulation is distributed among activators of FLO11 allowing tuning of population-level heterogeneity in its expression.
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DOI：
10.1371/journal.pgen.1000673
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发表时间：
2009-10
期刊：
影响因子：
4.5
通讯作者：
Maheshri N
中科院分区：
文献类型：
--
作者：
Octavio LM;Gedeon K;Maheshri N
表观遗传开关通常通过DNA或组蛋白的共价修饰在局部编码它们的状态信息，或者通常在反式调节因子的水平上在全局编码它们的状态信息。在这里，我们研究如何调控顺式编码的表观遗传开关控制基因表达的异质性的程度，这是最终在人口中的表型多样性。我们发现，在酿酒酵母中的FLO 11基因座的两个副本之间的开关沉默和主管启动子状态在一个随机和独立的方式，这意味着分子事件导致的过渡发生在本地的启动子，在顺式。我们进一步量化了反式调节剂对沉默和主管启动子状态之间的缓慢表观遗传转换以及与FLO 11的常规调节相关的快速启动子转换的影响。我们发现不同类型的调节器会影响表观遗传、传统或两种形式的调节。表观遗传沉默和常规基因激活的分布动力学控制为细胞在群体内形成基因表达和表型的分布提供了灵活性。在一个不确定和不断变化的世界中，具有多种表型的微生物种群可能会胜过单一种群。经过许多代，突变可以导致种群的遗传多样性。然而，微生物有快速产生这种多样性的策略。例如，如果多个基因缓慢地、随机地并且彼此独立地开启和关闭，那么基因表达状态的大组合以及因此的表型是可能的。不同的基因表达状态不涉及DNA序列的变化，因此是表观遗传的。我们发现，在S.酿酒酵母可以缓慢而独立地开启和关闭。此外，我们揭示了一种简单的调控策略，通过这种策略，细胞可以控制不同基因表达状态的细胞比例。由于FLO 11编码一种负责介导细胞-细胞和细胞-表面相互作用的细胞壁蛋白，这种控制可能确实允许自然群体中有一部分可控的细胞“粘在”周围，而另一部分很容易被冲走。
Epigenetic switches encode their state information either locally, often via covalent modification of DNA or histones, or globally, usually in the level of a trans-regulatory factor. Here we examine how the regulation of cis-encoded epigenetic switches controls the extent of heterogeneity in gene expression, which is ultimately tied to phenotypic diversity in a population. We show that two copies of the FLO11 locus in Saccharomyces cerevisiae switch between a silenced and competent promoter state in a random and independent fashion, implying that the molecular event leading to the transition occurs locally at the promoter, in cis. We further quantify the effect of trans regulators both on the slow epigenetic transitions between a silenced and competent promoter state and on the fast promoter transitions associated with conventional regulation of FLO11. We find different classes of regulators affect epigenetic, conventional, or both forms of regulation. Distributing kinetic control of epigenetic silencing and conventional gene activation offers cells flexibility in shaping the distribution of gene expression and phenotype within a population. In an uncertain and changing world, microbial populations with a diverse range of phenotypes may outperform a monolithic population. Over many generations, mutations can lead to genetic diversity in a population. However, microbes have strategies to generate such diversity quickly. For example, if multiple genes switch ON and OFF slowly, randomly, and independently of each other, then a large combination of gene expression states, and hence phenotypes, are possible. The different gene expression states do not involve changes in DNA sequence and are therefore epigenetically inherited. We show that the two copies of the FLO11 gene in S. cerevisiae can switch ON and OFF slowly and independently. In addition, we reveal a simple regulatory strategy by which cells can control the proportion of cells in different gene expression states. Because FLO11 encodes a cell-wall protein responsible for mediating cell–cell and cell–surface interactions, this control might literally allow natural populations to have a controllable fraction of cells “stick around” while the other fraction is easily washed away.
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