Whole-genome analysis of 5-hydroxymethylcytosine and 5-methylcytosine at base resolution in the human brain.
Whole-genome analysis of 5-hydroxymethylcytosine and 5-methylcytosine at base resolution in the human brain.
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人脑中 5-羟甲基胞嘧啶和 5-甲基胞嘧啶碱基分辨率的全基因组分析
DOI：
10.1186/gb-2014-15-3-r49
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发表时间：
2014-03-04
期刊：
影响因子：
12.3
通讯作者：
Qiao J
中科院分区：
文献类型：
--
作者：
Wen L;Li X;Yan L;Tan Y;Li R;Zhao Y;Wang Y;Xie J;Zhang Y;Song C;Yu M;Liu X;Zhu P;Li X;Hou Y;Guo H;Wu X;He C;Li R;Tang F;Qiao J
背景5-甲基胞嘧啶（mC）可以被四甲基胞嘧啶双加氧酶（Tet）家族氧化为5-羟甲基胞嘧啶（hmC），5-羟甲基胞嘧啶（hmC）是mC去甲基化的中间体，也可能是影响染色质结构的稳定表观遗传修饰。 hmC 在哺乳动物大脑中特别丰富，但其功能目前尚不清楚。需要高分辨率羟甲基化图谱才能充分了解 hmC 在人脑中的功能。结果我们通过联合应用 Tet 辅助亚硫酸氢盐测序和亚硫酸氢盐测序，展示了人脑中 hmC 和 mC 的全基因组和单碱基分辨率图谱。我们证明 hmC 从胎儿阶段到成年阶段显着增加，并且在成年大脑中，所有 CpG 的 13% 高度羟甲基化，在基因区域和远端调控元件处强烈富集。值得注意的是，hmC 峰位于外显子-内含子边界的 5' 剪接位点，表明 hmC 和剪接之间存在机械联系。我们报告了令人惊讶的与转录相关的 hmC 偏向基因体的有义链和 mC 偏向基因体的反义链。此外，hmC 与 H3K27me3 标记和 H3K9me3 标记的抑制基因组区域呈负相关，并且在平衡增强子中比活性增强子更富集。结论我们提供了人脑中的单碱基分辨率 hmC 和 mC 图谱，我们的数据暗示了 hmC 在调节剪接和基因表达中的新作用。羟甲基化是位于平衡增强子和活跃转录区域的大部分 CpG 的主要修饰状态，表明其在这些区域的表观遗传调节中发挥作用。
Background5-methylcytosine (mC) can be oxidized by the tet methylcytosine dioxygenase (Tet) family of enzymes to 5-hydroxymethylcytosine (hmC), which is an intermediate of mC demethylation and may also be a stable epigenetic modification that influences chromatin structure. hmC is particularly abundant in mammalian brains but its function is currently unknown. A high-resolution hydroxymethylome map is required to fully understand the function of hmC in the human brain.ResultsWe present genome-wide and single-base resolution maps of hmC and mC in the human brain by combined application of Tet-assisted bisulfite sequencing and bisulfite sequencing. We demonstrate that hmCs increase markedly from the fetal to the adult stage, and in the adult brain, 13% of all CpGs are highly hydroxymethylated with strong enrichment at genic regions and distal regulatory elements. Notably, hmC peaks are identified at the 5′splicing sites at the exon-intron boundary, suggesting a mechanistic link between hmC and splicing. We report a surprising transcription-correlated hmC bias toward the sense strand and an mC bias toward the antisense strand of gene bodies. Furthermore, hmC is negatively correlated with H3K27me3-marked and H3K9me3-marked repressive genomic regions, and is more enriched at poised enhancers than active enhancers.ConclusionsWe provide single-base resolution hmC and mC maps in the human brain and our data imply novel roles of hmC in regulating splicing and gene expression. Hydroxymethylation is the main modification status for a large portion of CpGs situated at poised enhancers and actively transcribed regions, suggesting its roles in epigenetic tuning at these regions.
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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：
3.7
作者：
Globisch D;Münzel M;Müller M;Michalakis S;Wagner M;Koch S;Brückl T;Biel M;Carell T
通讯作者：
Carell T
影响因子：
44.1
作者：
通讯作者：
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5-羟甲基胞嘧啶在小鼠精子发生过程中的动态
影响因子：
16.6
作者：
Gan, Haiyun;Wen, Lu;Tang, Fuchou
通讯作者：
Tang, Fuchou
影响因子：
64.5
作者：
Braunschweig U;Gueroussov S;Plocik AM;Graveley BR;Blencowe BJ
通讯作者：
Blencowe BJ