TY - JOUR
T1 - Epigenomic landscape of 5-hydroxymethylcytosine reveals its transcriptional regulation of lncRNAs in colorectal cancer
AU - Hu, Hanyang
AU - Shu, Maoguo
AU - He, Lin
AU - Yu, Xueyuan
AU - Liu, Xiangyu
AU - Lu, Yalin
AU - Chen, Yinghong
AU - Miao, Xiaoping
AU - Chen, Xiaohua
N1 - Publisher Copyright:
© 2017 Cancer Research UK. All rights reserved.
PY - 2017/2/28
Y1 - 2017/2/28
N2 - Background: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).Methods:We integrated genome-wide profiles of 5hmC, 5mC, transcriptome and histone marks in CRC patients and examined the 5hmC-based clinical outcomes in patients.Results: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.Conclusions:5-hydroxymethylcytosine is critical in regulating the transcription of lncRNA and serve as novel biomarkers for clinical prognosis in CRC.
AB - Background: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).Methods:We integrated genome-wide profiles of 5hmC, 5mC, transcriptome and histone marks in CRC patients and examined the 5hmC-based clinical outcomes in patients.Results: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.Conclusions:5-hydroxymethylcytosine is critical in regulating the transcription of lncRNA and serve as novel biomarkers for clinical prognosis in CRC.
UR - https://www.scopus.com/pages/publications/85011298837
U2 - 10.1038/bjc.2016.457
DO - 10.1038/bjc.2016.457
M3 - 文章
C2 - 28141796
AN - SCOPUS:85011298837
SN - 0007-0920
VL - 116
SP - 658
EP - 668
JO - British Journal of Cancer
JF - British Journal of Cancer
IS - 5
ER -
