Chromatin Remodeling in Mammary Gland Differentiation and Breast Tumorigenesis
Chromatin Remodeling in Mammary Gland Differentiation and Breast Tumorigenesis
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DOI：
10.1101/cshperspect.a004515
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发表时间：
2010-09-01
影响因子：
7.2
通讯作者：
Esteller, Manel
中科院分区：
文献类型：
--
作者：
Huang, Tim H. -M.;Esteller, Manel
DNA 甲基化和组蛋白修饰在重塑乳腺干/祖细胞多谱系分化所需基因的染色质结构中发挥重要作用。这种明确的表观遗传编程的作用是在分化后代的多次细胞分裂中遗传地维持这些基因座的转录可塑性。长期暴露于异雌激素或炎症微环境的祖细胞中，表观遗传事件可能会失调。此外，表观遗传介导的与肿瘤抑制相关的基因沉默可能发生，导致未分化或半分化细胞的克隆增殖。或者，负向调节其蛋白质编码靶标表达的 microRNA 可能会受到表观遗传抑制，导致这些基因的致癌表达。在这里，我们进一步讨论 DNA 甲基化和组蛋白修饰之间的相互作用，这些相互作用对乳腺干细胞/祖细胞的分化以及肿瘤的发生和进展具有重要作用。
DNA methylation and histone modifications have essential roles in remodeling chromatin structure of genes necessary for multi-lineage differentiation of mammary stem/progenitor cells. The role of this well-defined epigenetic programming is to heritably maintain transcriptional plasticity of these loci over multiple cell divisions in the differentiated progeny. Epigenetic events can be deregulated in progenitor cells chronically exposed to xenoestrogen or inflammatory microenvironment. In addition, epigenetically mediated silencing of genes associated with tumor suppression can take place, resulting in clonal proliferation of undifferentiated or semidifferentiated cells. Alternatively, microRNAs that negatively regulate the expression of their protein-coding targets may become epigenetically repressed, leading to oncogenic expression of these genes. Here we further discuss interactions between DNA methylation and histone modifications that have significant contributions to the differentiation of mammary stem/progenitor cells and to tumor initiation and progression.