Whole-genome bisulfite sequencing of multiple individuals reveals complementary roles of promoter and gene body methylation in transcriptional regulation.
Whole-genome bisulfite sequencing of multiple individuals reveals complementary roles of promoter and gene body methylation in transcriptional regulation.
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DOI：
10.1186/s13059-014-0408-0
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发表时间：
2014-07-30
期刊：
影响因子：
12.3
通讯作者：
Yip KY
中科院分区：
文献类型：
--
作者：
Lou S;Lee HM;Qin H;Li JW;Gao Z;Liu X;Chan LL;Kl Lam V;So WY;Wang Y;Lok S;Wang J;Ma RC;Tsui SK;Chan JC;Chan TF;Yip KY
DNA甲基化是参与基因调控的表观遗传修饰的重要类型。虽然启动子处的强DNA甲基化被广泛认为与转录抑制有关，但DNA甲基化的许多方面仍未完全了解，包括DNA甲基化和表达水平之间的定量关系，以及启动子和基因体甲基化的各自作用。在这里，我们对来自人类样本和细胞系的全基因组亚硫酸氢盐测序和 RNA 测序数据进行了综合分析。我们发现，虽然通常观察到启动子甲基化与基因表达呈负相关，但只有在 DNA 甲基化水平非常高的基因上，抑制作用才明显。通过统计模型，我们发现DNA甲基化一般可以指示基因的表达类别，但基因体甲基化是比启动子甲基化更好的指标。这些发现具有普遍性，因为从样本或细胞系构建的模型可以准确地拟合来自另一个样本或细胞系的看不见的数据。我们进一步发现启动子和基因体甲基化具有最小的冗余，并且任何一个都足以表明低表达。最后，我们通过将组蛋白修饰数据与 DNA 甲基化数据整合来获得增强的建模能力，表明两种类型的信息都不能完全包含另一种信息。我们的结果表明启动子外部的 DNA 甲基化在基因调控中也发挥着关键作用。未来关于基因调控机制和疾病相关差异甲基化的研究应更多关注基因体和其他非启动子区域的DNA甲基化。本文的在线版本 (doi:10.1186/s13059-014-0408-0) 包含补充材料，可供授权用户使用。
DNA methylation is an important type of epigenetic modification involved in gene regulation. Although strong DNA methylation at promoters is widely recognized to be associated with transcriptional repression, many aspects of DNA methylation remain not fully understood, including the quantitative relationships between DNA methylation and expression levels, and the individual roles of promoter and gene body methylation. Here we present an integrated analysis of whole-genome bisulfite sequencing and RNA sequencing data from human samples and cell lines. We find that while promoter methylation inversely correlates with gene expression as generally observed, the repressive effect is clear only on genes with a very high DNA methylation level. By means of statistical modeling, we find that DNA methylation is indicative of the expression class of a gene in general, but gene body methylation is a better indicator than promoter methylation. These findings are general in that a model constructed from a sample or cell line could accurately fit the unseen data from another. We further find that promoter and gene body methylation have minimal redundancy, and either one is sufficient to signify low expression. Finally, we obtain increased modeling power by integrating histone modification data with the DNA methylation data, showing that neither type of information fully subsumes the other. Our results suggest that DNA methylation outside promoters also plays critical roles in gene regulation. Future studies on gene regulatory mechanisms and disease-associated differential methylation should pay more attention to DNA methylation at gene bodies and other non-promoter regions. The online version of this article (doi:10.1186/s13059-014-0408-0) contains supplementary material, which is available to authorized users.
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影响因子：
46.9
作者：
Ball, Madeleine P.;Li, Jin Billy;Gao, Yuan;Lee, Je-Hyuk;LeProust, Emily M.;Park, In-Hyun;Xie, Bin;Daley, George Q.;Church, George M.
通讯作者：
Church, George M.
影响因子：
7
作者：
Harrow J;Frankish A;Gonzalez JM;Tapanari E;Diekhans M;Kokocinski F;Aken BL;Barrell D;Zadissa A;Searle S;Barnes I;Bignell A;Boychenko V;Hunt T;Kay M;Mukherjee G;Rajan J;Despacio-Reyes G;Saunders G;Steward C;Harte R;Lin M;Howald C;Tanzer A;Derrien T;Chrast J;Walters N;Balasubramanian S;Pei B;Tress M;Rodriguez JM;Ezkurdia I;van Baren J;Brent M;Haussler D;Kellis M;Valencia A;Reymond A;Gerstein M;Guigó R;Hubbard TJ
通讯作者：
Hubbard TJ
DOI：
10.1073/pnas.93.16.8334
发表时间：
1996-08-06
影响因子：
11.1
作者：
Hohn, T;Corsten, S;Rothnie, H
通讯作者：
Rothnie, H
影响因子：
12.3
作者：
Flanagan, James M;Wild, Laurence
通讯作者：
Wild, Laurence
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y