|Whole-genome analysis of 5-hydroxymethylcytosine and 5-methylcytosine at base resolution in the human brain|
|Wen, Lu1,2; Li, Xianlong1,2; Yan, Liying1,2,3; Tan, Yuexi1,2; Li, Rong1,2,3; Zhao, Yangyu1,2,3; Wang, Yan1,2,3; Xie, Jingcheng4; Zhang, Yan1,2,3; Song, Chunxiao5,6; Yu, Miao5,6; Liu, Xiaomeng1,2; Zhu, Ping1,2; Li, Xiaoyu8; Hou, Yu1,2; Guo, Hongshan1,2; Wu, Xinglong1,2; He, Chuan5,6; Li, Ruiqiang1,2,8; Tang, Fuchou1,2,7; Qiao, Jie1,2,3|
|WOS标题词||Science & Technology|
|类目[WOS]||Biotechnology & Applied Microbiology ; Genetics & Heredity|
|研究领域[WOS]||Biotechnology & Applied Microbiology ; Genetics & Heredity|
|关键词[WOS]||EMBRYONIC STEM-CELLS ; DNA-METHYLATION ; GENE-EXPRESSION ; MAMMALIAN DNA ; TET1 ; 5-CARBOXYLCYTOSINE ; METHYLOME ; ENHANCERS ; CHROMATIN ; DYNAMICS|
Background: 5-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.
Results: We 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.
Conclusions: We 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.
|项目编号||2011CB944504 ; 2012CB966704 ; 2011CB966303 ; 31230047 ; 31322037 ; 31271543|
|资助机构||National Basic Research Program of China ; National Natural Science of China|
|作者单位||1.Minist Educ, Key Lab Assisted Reprod, Beijing 100191, Peoples R China|
2.Univ Chicago, Dept Chem, Chicago, IL 60637 USA
3.Peking Univ, Hosp 3, Coll Life Sci, Biodynam Opt Imaging Ctr, Beijing 100871, Peoples R China
4.Peking Univ, Hosp 3, Coll Life Sci, Ctr Reprod Med, Beijing 100871, Peoples R China
5.Peking Univ, Hosp 3, Dept Neurosurg, Beijing 100191, Peoples R China
6.Univ Chicago, Inst Biophys Dynam, Chicago, IL 60637 USA
7.Minist Educ, Key Lab Cell Proliferat & Differentiat, Beijing 100871, Peoples R China
8.Peking Univ, Coll Life Sci, Peking Tsinghua Ctr Life Sci, Beijing 100871, Peoples R China
|Wen, Lu,Li, Xianlong,Yan, Liying,et al. Whole-genome analysis of 5-hydroxymethylcytosine and 5-methylcytosine at base resolution in the human brain[J]. GENOME BIOLOGY,2014,15(3).|
|APA||Wen, Lu.,Li, Xianlong.,Yan, Liying.,Tan, Yuexi.,Li, Rong.,...&Qiao, Jie.(2014).Whole-genome analysis of 5-hydroxymethylcytosine and 5-methylcytosine at base resolution in the human brain.GENOME BIOLOGY,15(3).|
|MLA||Wen, Lu,et al."Whole-genome analysis of 5-hydroxymethylcytosine and 5-methylcytosine at base resolution in the human brain".GENOME BIOLOGY 15.3(2014).|