Characterization of tissue-specific differential DNA methylation suggests distinct modes of positive and negative gene expression regulation.
Characterization of tissue-specific differential DNA methylation suggests distinct modes of positive and negative gene expression regulation.
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组织特异性差异DNA甲基化的特征表明存在正负基因表达调控的不同模式。
DOI：
10.1186/s12864-015-1271-4
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发表时间：
2015-02-05
期刊：
影响因子：
4.4
通讯作者：
Qian J
中科院分区：
文献类型：
--
作者：
Wan J;Oliver VF;Wang G;Zhu H;Zack DJ;Merbs SL;Qian J
DNA甲基化在许多生物过程中调控基因表达起着重要作用。然而，dna甲基化依赖性基因调控的机制尚不完全清楚。在这里，我们探讨了两种可能的DNA甲基化调控机制与相反的基因表达调控模式。通过比较不同组织的全基因组甲基化和表达模式，我们发现大多数组织特异性差异甲基化区域（T-DMRs）与其相关基因的表达呈负相关（负T-DMRs），这与DNA甲基化抑制基因表达的经典教条一致；然而，很大一部分T-DMRs与基因表达呈正相关（阳性T-DMRs）。我们观察到，阳性T-DMRs与阴性T-DMRs具有相似的基因组位置，除了阳性T-DMRs在启动子区域更丰富。阳性和阴性的T-DMRs都富含dna酶I超敏位点（DHSs），这表明两者都可能是功能性的。阳性和阴性T-DMRs的CpG位点也比基因组背景更具进化保守性。有趣的是，假设的阳性T-DMR靶基因富集了转录抑制因子等负调节因子，这表明通过转录抑制因子间接抑制DNA甲基化表达的新模式。同样，阳性和阴性T-DMRs存在两组不同的DNA序列基序，这表明两组不同的转录因子（TFs）参与DNA甲基化介导的阳性和阴性调节。我们发现T-DMRs与基因表达呈负相关和正相关，这意味着存在两种不同的DNA甲基化依赖性基因调控机制。本文的在线版本（doi:10.1186/s12864-015-1271-4）包含补充材料，可供授权用户使用。
DNA methylation plays an important role in regulating gene expression during many biological processes. However, the mechanism of DNA-methylation-dependent gene regulation is not fully understood. Here, we explore two possible DNA methylation regulatory mechanisms with opposite modes of gene expression regulation. By comparing the genome-wide methylation and expression patterns in different tissues, we find that majority of tissue-specific differentially methylated regions (T-DMRs) are negatively correlated with expression of their associated genes (negative T-DMRs), consistent with the classical dogma that DNA methylation suppresses gene expression; however, a significant portion of T-DMRs are positively correlated with gene expression (positive T-DMRs). We observe that the positive T-DMRs have similar genomic location as negative T-DMRs, except that the positive T-DMRs are more enriched in the promoter regions. Both positive and negative T-DMRs are enriched in DNase I hypersensitivity sites (DHSs), suggesting that both are likely to be functional. The CpG sites of both positive and negative T-DMRs are also more evolutionarily conserved than the genomic background. Interestingly, the putative target genes of the positive T-DMR are enriched for negative regulators such as transcriptional repressors, suggesting a novel mode of indirect DNA methylation inhibition of expression through transcriptional repressors. Likewise, two distinct sets of DNA sequence motifs exist for positive and negative T-DMRs, suggesting that two distinct sets of transcription factors (TFs) are involved in positive and negative regulation mediated by DNA methylation. We find both negative and positive association between T-DMRs and gene expression, which implies the existence of two different mechanisms of DNA methylation-dependent gene regulation. The online version of this article (doi:10.1186/s12864-015-1271-4) contains supplementary material, which is available to authorized users.
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影响因子：
30.8
作者：
John S;Sabo PJ;Thurman RE;Sung MH;Biddie SC;Johnson TA;Hager GL;Stamatoyannopoulos JA
通讯作者：
Stamatoyannopoulos JA
影响因子：
7.7
作者：
Hu S;Wan J;Su Y;Song Q;Zeng Y;Nguyen HN;Shin J;Cox E;Rho HS;Woodard C;Xia S;Liu S;Lyu H;Ming GL;Wade H;Song H;Qian J;Zhu H
通讯作者：
Zhu H
R环的形成是未甲基化的人类CpG岛启动子的独特特征。
影响因子：
16
作者：
Ginno PA;Lott PL;Christensen HC;Korf I;Chédin F
通讯作者：
Chédin F
影响因子：
64.8
作者：
Shen, Yin;Yue, Feng;McCleary, David F.;Ye, Zhen;Edsall, Lee;Kuan, Samantha;Wagner, Ulrich;Dixon, Jesse;Lee, Leonard;Lobanenkov, Victor V.;Ren, Bing
通讯作者：
Ren, Bing
影响因子：
3.9
作者：
Oliver VF;Wan J;Agarwal S;Zack DJ;Qian J;Merbs SL
通讯作者：
Merbs SL