A comparative analysis of DNA methylation across human embryonic stem cell lines.
A comparative analysis of DNA methylation across human embryonic stem cell lines.
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DOI：
10.1186/gb-2011-12-7-r62
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发表时间：
2011-07-06
期刊：
影响因子：
12.3
通讯作者：
Pellegrini M
中科院分区：
文献类型：
--
作者：
Chen PY;Feng S;Joo JW;Jacobsen SE;Pellegrini M
我们对三个人胚胎干细胞（HESC）系的全基因组DNA甲基化谱进行了比较分析。先前已经表明，HESC系具有比分化细胞显著更高的非CG甲基化，因此我们询问这些位点是否在细胞系中是保守的。我们发现，高度甲基化的非CG位点是高度保守的，特别是当发现在基序TACAG。它们富含剪接位点，并且比基因中的其他非CG位点甲基化程度更高。我们接下来研究了等位基因特异性表达和等位基因特异性甲基化之间的关系。通过结合亚硫酸氢盐测序和全转录组鸟枪测序（RNA-seq）数据，我们确定了1,020个显示等位基因特异性表达的基因，全基因组14%的CG位点具有等位基因特异性甲基化。最后，我们询问转录因子结合位点的甲基化状态是否影响转录因子的结合。我们确定了结合位点甲基化水平的变化，并发现对于几种转录因子，结合位点甲基化与基因表达之间的相关性通常比相邻序列更强。这些结果表明，高度甲基化的保守的非CG位点在HESC的调节中可能发挥功能性作用，但目前尚不清楚。我们还鉴定了一组新的基因，它们可能以等位基因特异性的方式通过甲基化进行转录调控。对转录因子结合位点的分析表明，顺式调控元件的甲基化状态影响因子结合和调控转录的能力。
We performed a comparative analysis of the genome-wide DNA methylation profiles from three human embryonic stem cell (HESC) lines. It had previously been shown that HESC lines had significantly higher non-CG methylation than differentiated cells, and we therefore asked whether these sites were conserved across cell lines. We find that heavily methylated non-CG sites are strongly conserved, especially when found within the motif TACAG. They are enriched in splice sites and are more methylated than other non-CG sites in genes. We next studied the relationship between allele-specific expression and allele-specific methylation. By combining bisulfite sequencing and whole transcriptome shotgun sequencing (RNA-seq) data we identified 1,020 genes that show allele-specific expression, and 14% of CG sites genome-wide have allele-specific methylation. Finally, we asked whether the methylation state of transcription factor binding sites affects the binding of transcription factors. We identified variations in methylation levels at binding sites and found that for several transcription factors the correlation between the methylation at binding sites and gene expression is generally stronger than in the neighboring sequences. These results suggest a possible but as yet unknown functional role for the highly methylated conserved non-CG sites in the regulation of HESCs. We also identified a novel set of genes that are likely transcriptionally regulated by methylation in an allele-specific manner. The analysis of transcription factor binding sites suggests that the methylation state of cis-regulatory elements impacts the ability of factors to bind and regulate transcription.
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影响因子：
56.9
作者：
Humpherys, D;Eggan, K;Jaenisch, R
通讯作者：
Jaenisch, R
影响因子：
30.8
作者：
Kolasinska-Zwierz P;Down T;Latorre I;Liu T;Liu XS;Ahringer J
通讯作者：
Ahringer J
影响因子：
56.9
作者：
Gregg, Christopher;Zhang, Jiangwen;Dulac, Catherine
通讯作者：
Dulac, Catherine
DOI：
10.1038/nrg2719
发表时间：
2010-03
期刊：
Nature reviews. Genetics
影响因子：
--
作者：
通讯作者：
--
影响因子：
56.9
作者：
Hellman, Asaf;Chess, Andrew
通讯作者：
Chess, Andrew