Genome-wide quantitative assessment of variation in DNA methylation patterns.
Genome-wide quantitative assessment of variation in DNA methylation patterns.
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DNA 甲基化模式变异的全基因组定量评估。
DOI：
10.1093/nar/gkr017
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发表时间：
2011-05
影响因子：
14.9
通讯作者：
Soares MB
中科院分区：
文献类型：
--
作者：
Xie H;Wang M;de Andrade A;Bonaldo Mde F;Galat V;Arndt K;Rajaram V;Goldman S;Tomita T;Soares MB
基因组DNA甲基化对哺乳动物发育和细胞分化的转录调控有实质性贡献。人们已经做了大量的努力来破译DNA甲基化模式的建立和维持的分子机制。然而，对DNA甲基化模式的全基因组变异知之甚少。在这项研究中，我们引入了甲基化熵的概念，一个衡量细胞群体中DNA甲基化模式的随机性，并利用它来评估Alu重复序列和启动子的DNA甲基化模式的变异性。进行了一些有趣的观察：（i）在细胞群体内，基因组基因座之间的甲基化熵不同;（ii）在细胞群体中，大多数基因组基因座的甲基化熵保持恒定;（iii）与正常组织对照相比，一些肿瘤表现出更大的甲基化熵;（iv）具有高甲基化熵的Alu元件与高GC含量相关，但与CpG二核苷酸的消耗相关，以及（v）位于内含子区或远离CpG岛的Alu元件与低甲基化熵相关。我们进一步鉴定了12个推定的等位基因特异性甲基化基因组基因座，包括4个Alu元件和8个启动子。最后，使用亚克隆的正常成纤维细胞，我们证明了高度可变的甲基化模式是由DNA甲基化遗传的低保真度引起的。
Genomic DNA methylation contributes substantively to transcriptional regulations that underlie mammalian development and cellular differentiation. Much effort has been made to decipher the molecular mechanisms governing the establishment and maintenance of DNA methylation patterns. However, little is known about genome-wide variation of DNA methylation patterns. In this study, we introduced the concept of methylation entropy, a measure of the randomness of DNA methylation patterns in a cell population, and exploited it to assess the variability in DNA methylation patterns of Alu repeats and promoters. A few interesting observations were made: (i) within a cell population, methylation entropy varies among genomic loci; (ii) among cell populations, the methylation entropies of most genomic loci remain constant; (iii) compared to normal tissue controls, some tumors exhibit greater methylation entropies; (iv) Alu elements with high methylation entropy are associated with high GC content but depletion of CpG dinucleotides and (v) Alu elements in the intronic regions or far from CpG islands are associated with low methylation entropy. We further identified 12 putative allelic-specific methylated genomic loci, including four Alu elements and eight promoters. Lastly, using subcloned normal fibroblast cells, we demonstrated the highly variable methylation patterns are resulted from low fidelity of DNA methylation inheritance.
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影响因子：
64.5
作者：
Okano, M;Bell, DW;Li, E
通讯作者：
Li, E
影响因子：
4.8
作者：
Vilkaitis, G;Suetake, I;Tajima, S
通讯作者：
Tajima, S
影响因子：
5.3
作者：
Liang, GG;Chan, MF;Jones, PA
通讯作者：
Jones, PA
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7
作者：
Ushijima, T;Watanabe, N;Miyamoto, K
通讯作者：
Miyamoto, K
影响因子：
56.9
作者：
Bostick, Magnolia;Kim, Jong Kyong;Jacobsen, Steven E.
通讯作者：
Jacobsen, Steven E.