DNA G-quadruplex stability, position and chromatin accessibility are associated with CpG island methylation
DNA G-quadruplex stability, position and chromatin accessibility are associated with CpG island methylation
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DOI：
10.1111/febs.15065
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发表时间：
2019-09-26
期刊：
影响因子：
5.4
通讯作者：
Peres Line, Sergio Roberto
中科院分区：
文献类型：
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作者：
Jara-Espejo, Manuel;Peres Line, Sergio Roberto
CpG 岛 (CGI) 是与基因启动子相关并参与基因表达调控的基因组区域。尽管它们的 CpG 含量很高并且与大量基因组 DNA 甲基化模式不同，但这些区域通常是低甲基化的。迄今为止，控制 CGI 甲基化模式的机制仍不清楚。 G-四联体（G4）结构可以抑制DNA甲基转移酶1的酶活性，导致CGI低甲基化。我们的目的是分析 G4 形成序列 (G4FS) 和 CGI 甲基化的关联，并确定可能调节这种现象的 G4FS 的内在和外在特征。使用来自人类胚胎干细胞 (hESC) 和三个 hESC 衍生群体的甲基化数据，我们发现位于 CGI (CGI/CpG) 内部的低甲基化 CpG 往往与高度稳定的 G4FS（最小自由能）相关。
CpG islands (CGI) are genomic regions associated with gene promoters and involved in gene expression regulation. Despite their high CpG content and unlike bulk genomic DNA methylation pattern, these regions are usually hypomethylated. So far, the mechanisms controlling the CGI methylation patterning remain unclear. G-quadruplex (G4) structures can inhibit DNA methyltransferases 1 enzymatic activity, leading to CGI hypomethylation. Our aim was to analyse the association of G4 forming sequences (G4FS) and CGI methylation as well as to determine the intrinsic and extrinsic characteristics of G4FS that may modulate this phenomenon. Using methylation data from human embryonic stem cells (hESCs) and three hESC-derived populations, we showed that hypomethylated CpGs located inside CGI (CGI/CpG) tend to be associated with highly stable G4FS (Minimum free energy