Aufsatz W, Stoiber T, Rakic B, Naumann K
Gregor Mendel Institute of Molecular Plant Biology, Austrian Academy of Sciences, Vienna, Austria.
Oncogene. 2007 Aug 13;26(37):5477-88. doi: 10.1038/sj.onc.1210615.
Epigenetic reprogramming is at the base of cancer initiation and progression. Generally, genome-wide reduction in cytosine methylation contrasts with the hypermethylation of control regions of functionally well-established tumor suppressor genes and many other genes whose role in cancer biology is not yet clear. While insight into mechanisms that induce aberrant cytosine methylation in cancer cells is just beginning to emerge, the initiating signals for analogous promoter methylation in plants are well documented. In Arabidopsis, the silencing of promoters requires components of the RNA interference machinery and promoter double-stranded RNA (dsRNA) to induce a repressive chromatin state that is characterized by cytosine methylation and histone deacetylation catalysed by the RPD3-type histone deacetylase AtHDA6. Similar mechanisms have been shown to occur in fission yeast and mammals. This review focuses on the connections between cytosine methylation, dsRNA and AtHDA6-controlled histone deacetylation during promoter silencing in Arabidopsis and discusses potential mechanistic similarities of these silencing events in cancer and plant cells.
表观遗传重编程是癌症起始和进展的基础。一般来说,全基因组胞嘧啶甲基化的减少与功能明确的肿瘤抑制基因以及许多在癌症生物学中作用尚不清楚的其他基因的调控区域的高甲基化形成对比。虽然对癌细胞中诱导异常胞嘧啶甲基化的机制的认识才刚刚开始出现,但植物中类似启动子甲基化的起始信号已有充分记录。在拟南芥中,启动子的沉默需要RNA干扰机制的组分和启动子双链RNA(dsRNA)来诱导一种抑制性染色质状态,其特征是由RPD3型组蛋白脱乙酰酶AtHDA6催化的胞嘧啶甲基化和组蛋白去乙酰化。类似的机制已在裂殖酵母和哺乳动物中被证明存在。本综述重点关注拟南芥启动子沉默过程中胞嘧啶甲基化、dsRNA和AtHDA6控制的组蛋白去乙酰化之间的联系,并讨论这些沉默事件在癌症和植物细胞中潜在的机制相似性。