Octavio Leah M, Gedeon Kamil, Maheshri Narendra
Computational and Systems Biology Initiative, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America.
PLoS Genet. 2009 Oct;5(10):e1000673. doi: 10.1371/journal.pgen.1000673. Epub 2009 Oct 2.
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.
表观遗传开关通过局部方式（通常是通过DNA或组蛋白的共价修饰）或全局方式（通常是在反式调节因子水平）编码其状态信息。在这里，我们研究顺式编码的表观遗传开关的调控如何控制基因表达的异质性程度，而这最终与群体中的表型多样性相关。我们表明，酿酒酵母中FLO11位点的两个拷贝以随机且独立的方式在沉默启动子状态和有活性启动子状态之间切换，这意味着导致转变的分子事件在顺式中于启动子处局部发生。我们进一步量化了反式调节因子对沉默启动子状态和有活性启动子状态之间缓慢表观遗传转变以及与FLO11传统调控相关的快速启动子转变的影响。我们发现不同类别的调节因子会影响表观遗传、传统或两种形式的调控。分配表观遗传沉默和传统基因激活的动力学控制为细胞在塑造群体内基因表达和表型分布方面提供了灵活性。
