Institute of Fundamental Technological Research, Polish Academy of Sciences, 02-106 Warsaw, Poland.
Phys Biol. 2013 Jun;10(3):035007. doi: 10.1088/1478-3975/10/3/035007. Epub 2013 Jun 4.
Bistable regulatory elements enhance heterogeneity in cell populations and, in multicellular organisms, allow cells to specialize and specify their fate. Our study demonstrates that in a system of bistable genetic switch, the noise characteristics control in which of the two epigenetic attractors the cell population will settle. We focus on two types of noise: the gene switching noise and protein dimerization noise. We found that the change of magnitudes of these noise components for one of the two competing genes introduces a large asymmetry of the protein stationary probability distribution and changes the relative probability of individual gene activation. Interestingly, an increase of noise associated with a given gene can either promote or suppress the activation of the gene, depending on the type of noise. Namely, each gene is repressed by an increase of its gene switching noise and activated by an increase of its protein-product dimerization noise. The observed effect was found robust to the large, up to fivefold deviations of the model parameters. In summary, we demonstrated that noise itself may determine the relative strength of the epigenetic attractors, which may provide a unique mode of control of cell fate decisions.
双稳态调控元件增强了细胞群体的异质性，并且在多细胞生物中，允许细胞专门化并指定其命运。我们的研究表明，在双稳态遗传开关系统中，噪声特征控制着细胞群体将在两个表观遗传吸引子中的哪一个中稳定下来。我们关注两种类型的噪声：基因开关噪声和蛋白质二聚化噪声。我们发现，两种竞争基因之一的这些噪声分量的幅度变化会导致蛋白质固定概率分布的很大不对称性，并改变单个基因激活的相对概率。有趣的是，与给定基因相关的噪声增加可以促进或抑制基因的激活，这取决于噪声的类型。即，每个基因都会受到其基因开关噪声的增加的抑制，而受到其蛋白质产物二聚化噪声的增加的激活。观察到的效应在模型参数高达五倍的大偏差下仍然稳健。总之，我们证明了噪声本身可能决定表观遗传吸引子的相对强度，这可能为细胞命运决定的控制提供一种独特的模式。
