Epigenetic gene expression noise and phenotypic diversification of clonal cell populations
Epigenetic gene expression noise and phenotypic diversification of clonal cell populations
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DOI：
10.1111/j.1432-0436.2007.00219.x
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发表时间：
2008-01-01
期刊：
影响因子：
2.9
通讯作者：
Paldi, Andras
中科院分区：
文献类型：
--
作者：
Neildez-Nguyen, Thi My Anh;Parisot, Aurelie;Paldi, Andras
在遗传相同的细胞培养物中自发出现表型异质性是一种经常观察到的现象，它提供了一个简单的体外实验系统来模拟体内分化的问题。在本研究中，我们研究了基因表达水平的随机变化是否有助于人类细胞的表型变化。我们已经应用了两个荧光编码基因的方法和两个报告基因的表达变异的人类细胞培养。我们已经量化了由全局、启动子特异性或表观遗传来源决定的基因表达变异的部分。这两种类型的变化似乎有助于，以不同的方式，克隆细胞群体的表型多样化。全局或启动子特异性基因表达噪声随着细胞应激而增加，并通过使基因表达水平多样化而有助于细胞多样性的出现。表观遗传机制通过稳定基因转录水平或通过加强沉默状态来增加细胞状态的稳健性。
Spontaneous emergence of phenotypic heterogeneity in cultures of genetically identical cells is a frequently observed phenomenon that provides a simple in vitro experimental system to model the problems of in vivo differentiation. In the present study, we have investigated whether stochastic variation of gene expression levels could contribute to phenotypic change in human cells. We have applied the two fluorescence-coding gene method and the expression variability of the two reporter genes to human cells in culture. We have quantified the portion of gene expression variation determined by global, promoter-specific, or by epigenetic sources. These two types of variation appear to contribute, in different ways, to the phenotypic diversification of clonal cell populations. Global, or promoter-specific, gene expression noise increases with cellular stress and contributes to the emergence of cellular diversity by diversifying the gene-expression levels. Epigenetic mechanisms act to increase the robustness of the cellular state by stabilizing gene transcription levels or by reinforcing the silenced state.