Department of Oncological Sciences, University of Utah School of Medicine, Salt Lake City, UT 84112, USA.
Curr Opin Cell Biol. 2013 Apr;25(2):177-83. doi: 10.1016/j.ceb.2013.01.007. Epub 2013 Feb 8.
The importance and role of the cellular epigenome in cell fating and development have been studied for decades. The epigenome encompasses a range of attributes including DNA methylation, histone modifications, and chromatin remodelers; together these components define the cellular transcriptome, identity, and function. The cellular epigenome is dynamic in response to environmental signals, modifiable during normal cell differentiation and is heritable in daughter cells. This plasticity, however, poses a risk for misregulation and may underlie a number of hereditary disorders, development defects, and cancer. Although the first epigenetic change described in cancer was gene hypomethylation [Holliday R, Jeggo PA: Mechanisms for changing gene expression and their possible relationship to carcinogenesis.Cancer Surv 1985, 4:557-581; Feinberg AP, Vogelstein B: Hypomethylation distinguishes genes of some human cancers from their normal counterparts.Nature 1983, 301:89-92], we know that cancers not only display global hypomethylation, but also, site-specific gene hypermethylation in addition to changes in chromatin modifications. Mechanisms explaining the sometimes paradoxical epigenetic changes observed in cancer, their contributions to tumor initiation and progression and how epigenetics relate to genetic events are poorly understood. In this review we will briefly discuss recent findings on the epigenomic states observed in colon cancer, in particular, how perturbations to the genome and epigenome together may contribute to initiation and progression of colon cancer.
几十年来，细胞表观基因组在细胞命运和发育中的重要性和作用一直受到研究。表观基因组包括一系列属性，包括 DNA 甲基化、组蛋白修饰和染色质重塑剂；这些成分共同定义了细胞转录组、身份和功能。细胞表观基因组是动态的，可响应环境信号，在正常细胞分化过程中可修饰，并可在子细胞中遗传。然而，这种可塑性存在失调的风险，可能是许多遗传性疾病、发育缺陷和癌症的基础。尽管在癌症中描述的第一个表观遗传变化是基因低甲基化[Holliday R，Jeggo PA：改变基因表达的机制及其与致癌作用的可能关系。癌症生存 1985，4：557-581；Feinberg AP，Vogelstein B：低甲基化区分了一些人类癌症的基因与其正常对应物。自然 1983，301：89-92]，但我们知道，癌症不仅表现出全基因组低甲基化，而且还存在特定基因的高甲基化，以及染色质修饰的变化。解释癌症中观察到的有时矛盾的表观遗传变化的机制、它们对肿瘤起始和进展的贡献以及表观遗传学与遗传事件的关系尚未得到很好的理解。在这篇综述中，我们将简要讨论最近在结肠癌中观察到的表观基因组状态的发现，特别是基因组和表观基因组的扰动如何共同促进结肠癌的起始和进展。
