Epigenomic landscape of 5-hydroxymethylcytosine reveals its transcriptional regulation of lncRNAs in colorectal cancer.
Epigenomic landscape of 5-hydroxymethylcytosine reveals its transcriptional regulation of lncRNAs in colorectal cancer.
复制标题
5-羟甲基胞嘧啶的表观基因组景观揭示了结直肠癌中 lncRNA 的转录调控
DOI：
10.1038/bjc.2016.457
复制
发表时间：
2017-02-28
影响因子：
8.8
通讯作者：
Chen X
中科院分区：
文献类型：
--
作者：
Hu H;Shu M;He L;Yu X;Liu X;Lu Y;Chen Y;Miao X;Chen X
DNA在胞嘧啶（5mC） 5位的甲基化可以通过10 - 11易位家族转化为5-羟甲基胞嘧啶（5hmC）。全球5hmC水平的下降被认为是各种癌症的标志。5-羟甲基胞嘧啶分布在蛋白质编码基因小体和启动子上；然而，5hmC在长链非编码rna （lncRNAs）中的作用和分布尚不清楚。我们研究了5hmC在结直肠癌（CRC）中lncrna的分布和调控作用。我们整合了CRC患者中5hmC、5mC、转录组和组蛋白标记的全基因组图谱，并检查了基于5hmC的患者临床结果。5-羟甲基胞嘧啶分布在lncRNA位点，与lncRNA转录呈正相关。失调的CRC lncrna由5hmC直接或通过5hmC修饰的典型增强子和超增强子及启动子的异常活性进行调节。此外，5hmC参与lncRNA位点上的远程染色质相互作用。最后，受差异5hmC标记调控的lncrna与患者不同的临床结局和肿瘤状态相关。5-羟甲基胞嘧啶在调节lncRNA的转录中发挥着关键作用，并可作为CRC临床预后的新型生物标志物。
DNA methylation at the 5 position of cytosine (5mC) can be converted to 5-hydroxymethylcytosine (5hmC) by the ten–eleven translocation family. The loss of global levels of 5hmC has been regarded as a hallmark in various cancers. 5-hydroxymethylcytosine is distributed at protein-coding gene bodies and promoters; however, the role and distribution of 5hmC at long non-coding RNAs (lncRNAs) is not clear. We investigated the distribution and regulatory roles of 5hmC for lncRNAs in colorectal cancer (CRC). We integrated genome-wide profiles of 5hmC, 5mC, transcriptome and histone marks in CRC patients and examined the 5hmC-based clinical outcomes in patients. 5-hydroxymethylcytosine was distributed at lncRNA loci and positively correlated with lncRNA transcription. Dysreulated CRC lncRNAs were regulated by 5hmC directly or through abnormal activities of typical and super-enhancers and promoters modified by 5hmC. In addition, 5hmC was involved in long-range chromatin interactions at lncRNA loci. Finally, lncRNAs regulated by differential 5hmC marks were correlated with different clinical outcomes and tumour status in patients. 5-hydroxymethylcytosine is critical in regulating the transcription of lncRNA and serve as novel biomarkers for clinical prognosis in CRC.