The concurrence of DNA methylation and demethylation is associated with transcription regulation.
The concurrence of DNA methylation and demethylation is associated with transcription regulation.
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DOI：
10.1038/s41467-021-25521-7
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发表时间：
2021-09-06
影响因子：
16.6
通讯作者：
Li W
中科院分区：
文献类型：
--
作者：
Shi J;Xu J;Chen YE;Li JS;Cui Y;Shen L;Li JJ;Li W
哺乳动物DNA甲基化组是由两个相互拮抗的过程形成的，即DNA甲基转移酶（DNMT）的甲基化和10 - 11易位（泰特）双加氧酶的去甲基化。尽管在过去的十年中，甲基化或去甲基化的动力学已经被深入研究，但它们相互作用对基因表达的直接影响仍然难以捉摸。在这里，我们通过亚硫酸氢盐测序的部分甲基化读数中未甲基化CpG的百分比来量化DNA甲基化和去甲基化的同时发生。在通过其与DNMT和泰特酶的共定位的强关联来验证“甲基化并发”之后，我们观察到甲基化并发与基因表达强相关。值得注意的是，肿瘤中甲基化并发升高与40~60%的肿瘤抑制基因的抑制有关，这不能单独用启动子高甲基化来解释。此外，甲基化并发性可用于将平均甲基化差异可忽略不计的大的甲基化不足区域分层为具有不同染色质可及性和基因调控模式的两个亚组。总之，甲基化并发代表了一个独特的甲基化度量重要的转录调控，是不同于传统的度量，如平均甲基化和甲基化变异。哺乳动物甲基化组的整体模式是由甲基化和去甲基化的变化形成的。在这里，作者描述了一种度量甲基化并发性，该度量甲基化并发性测量了部分甲基化读段内未甲基化CpG的比例，并表明甲基化并发性与表观遗传学调控的肿瘤抑制基因相关。
The mammalian DNA methylome is formed by two antagonizing processes, methylation by DNA methyltransferases (DNMT) and demethylation by ten-eleven translocation (TET) dioxygenases. Although the dynamics of either methylation or demethylation have been intensively studied in the past decade, the direct effects of their interaction on gene expression remain elusive. Here, we quantify the concurrence of DNA methylation and demethylation by the percentage of unmethylated CpGs within a partially methylated read from bisulfite sequencing. After verifying ‘methylation concurrence’ by its strong association with the co-localization of DNMT and TET enzymes, we observe that methylation concurrence is strongly correlated with gene expression. Notably, elevated methylation concurrence in tumors is associated with the repression of 40~60% of tumor suppressor genes, which cannot be explained by promoter hypermethylation alone. Furthermore, methylation concurrence can be used to stratify large undermethylated regions with negligible differences in average methylation into two subgroups with distinct chromatin accessibility and gene regulation patterns. Together, methylation concurrence represents a unique methylation metric important for transcription regulation and is distinct from conventional metrics, such as average methylation and methylation variation. The global pattern of the mammalian methylome is formed by changes in methylation and demethylation. Here the authors describe a metric methylation concurrence that measures the ratio of unmethylated CpGs inside the partially methylated reads and show that methylation concurrence is associated with epigenetically regulated tumour suppressor genes.
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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：
12.3
作者：
Gu T;Lin X;Cullen SM;Luo M;Jeong M;Estecio M;Shen J;Hardikar S;Sun D;Su J;Rux D;Guzman A;Lee M;Qi LS;Chen JJ;Kyba M;Huang Y;Chen T;Li W;Goodell MA
通讯作者：
Goodell MA
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影响因子：
3.7
作者：
Cao J;Zhu S;Zhou W;Li J;Liu C;Xuan H;Yan J;Zheng L;Zhou L;Yu J;Chen G;Huang Y;Yu Z;Feng L
通讯作者：
Feng L
影响因子：
16
作者：
Cao, R;Zhang, Y
通讯作者：
Zhang, Y
影响因子：
16
作者：
Heinz S;Benner C;Spann N;Bertolino E;Lin YC;Laslo P;Cheng JX;Murre C;Singh H;Glass CK
通讯作者：
Glass CK