Chuang Jody C, Jones Peter A
Department of Biochemistry and Molecular Biology, USC/Norris Comprehensive Cancer Center, University of Southern California, Los Angeles 90089, USA.
Pediatr Res. 2007 May;61(5 Pt 2):24R-29R. doi: 10.1203/pdr.0b013e3180457684.
Epigenetics is defined as mitotically and meiotically heritable changes in gene expression that do not involve a change in the DNA sequence. Two major areas of epigenetics-DNA methylation and histone modifications-are known to have profound effects on controlling gene expression. DNA methylation is involved in normal cellular control of expression, and aberrant hypermethylation can lead to silencing of tumor-suppressor genes in carcinogenesis. Histone modifications control the accessibility of the chromatin and transcriptional activities inside a cell. MicroRNAs (miRNAs) are small RNA molecules, approximately 22 nucleotides long that can negatively control their target gene expression posttranscriptionally. There are currently more than 460 human miRNAs known, and the total number is predicted to be much larger. Recently, the expression of miRNAs has been definitively linked to cancer development, and miRNA profiles can be used to classify human cancers. miRNAs are encoded in our genome and are generally transcribed by RNA polymerase II. Despite the growing evidence for their importance in normal physiology, little is known about the regulation of miRNA expression. In this review, we will examine the relationship between miRNAs and epigenetics. We examine the effects of miRNAs on epigenetic machinery, and the control of miRNA expression by epigenetic mechanisms. Epigenetics is defined as heritable changes in gene expression that do not involve a change in DNA sequence.
表观遗传学的定义是基因表达中可通过有丝分裂和减数分裂遗传的变化，且这种变化不涉及DNA序列的改变。已知表观遗传学的两个主要领域——DNA甲基化和组蛋白修饰——对控制基因表达有深远影响。DNA甲基化参与基因表达的正常细胞调控，异常的高甲基化可导致肿瘤抑制基因在致癌过程中沉默。组蛋白修饰控制染色质的可及性以及细胞内的转录活性。微小RNA（miRNA）是小RNA分子，长度约为22个核苷酸，可在转录后对其靶基因表达进行负调控。目前已知的人类miRNA超过460种，预计总数会更多。最近，miRNA的表达已明确与癌症发展相关，miRNA谱可用于对人类癌症进行分类。miRNA在我们的基因组中编码，通常由RNA聚合酶II转录。尽管越来越多的证据表明它们在正常生理过程中很重要，但对miRNA表达的调控却知之甚少。在本综述中，我们将研究miRNA与表观遗传学之间的关系。我们将探讨miRNA对表观遗传机制的影响，以及表观遗传机制对miRNA表达的调控。表观遗传学的定义是基因表达中可遗传的变化，且这种变化不涉及DNA序列的改变。
