nature-genetic201211-3

来自以色列魏兹曼研究所的Amos Tanay及其同事在细胞群体中确定了DNA甲基化多态性的特点,并跟踪了体外培养超过300代的永生纤维母细胞,结果发现DNA上的差异甲基化区域是通过一随机机制和几乎确定的表观遗传重塑过程而形成的。相关的研究论文于10月14日在线发表在《Nature Genetics》期刊上。

-2012年11月《自然-遗传》

中文翻译


【题目】正常组织和癌症组织的差异甲基化区域的表观遗传多态性及其随机形成机制

【译文】DNA甲基化已经成为区别正常细胞与癌细胞的综合性图谱,但是细胞形成、维持和重编程差异甲基化区域的动态过程仍然难以描述。本研究发现来自异质的和多态的体细胞组织的细胞群体的甲基化模式。借助对体外培养超过300代的永生纤维母细胞的进化研究,我们追踪到将发展为显著不同的甲基化的均一染色体区域上动态变化的多态甲基化作用。这些数据表明群体-平均的甲基化变化,是通过产生大量局部和不相关的甲基化异常现象的随机过程而发生的。尽管这一过程具有随机性,但是几乎可以确定的是,基因位点均会发生表观遗传重塑,无论该位点是否具有对甲基化积累的耐性。细胞对甲基化积累的敏感性变化与组蛋白修饰程度和CCCTC-结合因子(CTCF)的占据变化有关。因此,鉴定细胞群体的表观遗传多态性是理解正常细胞与癌细胞甲基化动态变化的关键。

英文原稿


[Title]: Epigenetic polymorphism and the stochastic formation of differentially methylated regions in normal and cancerous tissues

[Authors]: Gilad Landan, Netta Mendelson Cohen, Zohar Mukamel, Amir Bar, Alina Molchadsky, Ran Brosh, Shirley Horn-Saban, Daniela Amann Zalcenstein, Naomi Goldfinger, Adi Zundelevich, Einav Nili Gal-Yam, Varda Rotter & Amos Tanay

[Abstract]: DNA methylation has been comprehensively profiled in normal and cancer cells, but the dynamics that form, maintain and reprogram differentially methylated regions remain enigmatic. Here, we show that methylation patterns within populations of cells from individual somatic tissues are heterogeneous and polymorphic. Using in vitro evolution of immortalized fibroblasts for over 300 generations, we track the dynamics of polymorphic methylation at regions developing significant differential methylation on average. The data indicate that changes in population-averaged methylation occur through a stochastic process that generates a stream of local and uncorrelated methylation aberrations. Despite the stochastic nature of the process, nearly deterministic epigenetic remodeling emerges on average at loci that lose or gain resistance to methylation accumulation. Changes in the susceptibility to methylation accumulation are correlated with changes in histone modification and CTCF occupancy. Characterizing epigenomic polymorphism within cell populations is therefore critical to understanding methylation dynamics in normal and cancer cells.

原文地址

http://www.nature.com/ng/journal/v44/n11/full/ng.2442.html

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