Department of Biomedical Engineering, Yale University, New Haven, CT 06511, USA.
Trends Biotechnol. 2011 Oct;29(10):517-25. doi: 10.1016/j.tibtech.2011.05.004. Epub 2011 Jun 21.
Gene expression noise is a significant source of phenotypic heterogeneity in otherwise identical populations of cells. Phenotypic heterogeneity can cause reversible drug resistance in diseased cells, and thus a better understanding of its origins might improve treatment strategies. In eukaryotes, data strongly suggest that intrinsic noise arises from transcriptional bursts caused by slow, random transitions between inactive and active gene states that are mediated by chromatin remodeling. In this review, we consider how chromatin modifications might modulate gene expression noise and lead to phenotypic diversity in diseases as varied as viral infection and cancer. Additionally, we argue that this fundamental information can be applied to develop innovative therapies that counteract 'pathogenic noise' and sensitize all diseased cells to therapeutic intervention.
基因表达噪声是造成相同细胞群体表现型异质性的一个重要因素。表型异质性可导致患病细胞产生可逆的药物抗性，因此，更好地了解其起源可能会改善治疗策略。在真核生物中，大量数据强烈表明，内在噪声源于转录爆发，而转录爆发是由缓慢、随机的基因状态从失活到激活的转变引起的，这种转变由染色质重塑介导。在这篇综述中，我们考虑了染色质修饰如何调节基因表达噪声，并导致从病毒感染和癌症等各种疾病中表现出的表型多样性。此外，我们还认为，这些基本信息可应用于开发创新性疗法，以对抗“致病噪声”并使所有患病细胞对治疗干预敏感。
