Macaluso Marcella, Giordano Antonio
Sbarro Institute for Cancer Research and Molecular Medicine, College of Science and Technology, Temple University, Philadelphia, PA, USA.
Tumori. 2004 Jul-Aug;90(4):367-72. doi: 10.1177/030089160409000401.
Since every cell of a multicellular organism contains the same genome, it is intriguing to understand why genetically homogenous cells are different from each other and what controls this. Several observations indicate that DNA methylation has an essential regulatory function in mammalian development, which is to establish the correct pattern of gene expression, and that DNA methylation pattern is tightly correlated with chromatin structure. Various physiological processes are controlled by specific DNA methylation patterns including genomic imprinting, inactivation of the X chromosome, regulation of tissue-specific gene expression and repression of transposons. Moreover, aberrant methylation could confer a selective advantage to cells, leading to cancerous growth. In this review we focus on the epigenetic molecular mechanisms during normal development and discuss how DNA methylation could affect the expression of genes leading to cancer transformation.
由于多细胞生物体的每个细胞都包含相同的基因组,因此理解基因同质的细胞为何彼此不同以及是什么控制这一点很有趣。一些观察结果表明,DNA甲基化在哺乳动物发育中具有重要的调节功能,即建立正确的基因表达模式,并且DNA甲基化模式与染色质结构密切相关。各种生理过程由特定的DNA甲基化模式控制,包括基因组印记、X染色体失活、组织特异性基因表达的调节和转座子的抑制。此外,异常甲基化可能赋予细胞选择性优势,导致癌性生长。在本综述中,我们关注正常发育过程中的表观遗传分子机制,并讨论DNA甲基化如何影响导致癌症转化的基因表达。