Genome-wide analysis of 5-hydroxymethylcytosine distribution reveals its dual function in transcriptional regulation in mouse embryonic stem cells
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TLDR
This study reveals the first genome-wide 5hmC distribution in pluripotent stem cells, and supports its dual function in regulating gene expression.Abstract:
Recent studies have demonstrated that the Ten-eleven translocation (Tet) family proteins can enzymatically convert 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC). While 5mC has been studied extensively, little is known about the distribution and function of 5hmC. Here we present a genome-wide profile of 5hmC in mouse embryonic stem (ES) cells. A combined analysis of global 5hmC distribution and gene expression profile in wild-type and Tet1-depleted ES cells suggests that 5hmC is enriched at both gene bodies of actively transcribed genes and extended promoter regions of Polycomb-repressed developmental regulators. Thus, our study reveals the first genome-wide 5hmC distribution in pluripotent stem cells, and supports its dual function in regulating gene expression.read more
Citations
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CpG Islands and the Regulation of Transcription
Aimee M. Deaton,Adrian Bird +1 more
TL;DR: Vertebrate CpG islands are generically equipped to influence local chromatin structure and simplify regulation of gene activity.
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Tet-Mediated Formation of 5-Carboxylcytosine and Its Excision by TDG in Mammalian DNA
Yu-Fei He,Bin-Zhong Li,Zheng Li,Peng Liu,Yang Wang,Qingyu Tang,Jianping Ding,Yingying Jia,Zhangcheng Chen,Lin Li,Yan Sun,Xiuxue Li,Qing Dai,Chun-Xiao Song,Kangling Zhang,Chuan He,Guoliang Xu +16 more
TL;DR: It is demonstrated that 5mC and 5hmC in DNA are oxidized to 5-carboxylcytosine (5caC) by Tet dioxygenases in vitro and in cultured cells, suggesting that oxidation of 5m C by Tet proteins followed by TDG-mediated base excision of 5caC constitutes a pathway for active DNA demethylation.
Journal ArticleDOI
TET-mediated active DNA demethylation: mechanism, function and beyond
Xiaoji Wu,Yi Zhang +1 more
TL;DR: Recent advances in biochemical and structural studies have revealed mechanistic insights into how TET and TDG mediate active DNA demethylation and many regulatory mechanisms of this process have been identified.
Journal ArticleDOI
Base-Resolution Analysis of 5-Hydroxymethylcytosine in the Mammalian Genome
Miao Yu,Gary C. Hon,Keith E. Szulwach,Chun-Xiao Song,Liang Zhang,Audrey Kim,Xuekun Li,Qing Dai,Yin Shen,Beomseok Park,Jung Hyun Min,Peng Jin,Bing Ren,Chuan He +13 more
TL;DR: Application of Tet-assisted bisulfite sequencing to embryonic stem cells not only confirms widespread distribution of 5hmC in the mammalian genome but also reveals sequence bias and strand asymmetry at5hmC sites.
Journal ArticleDOI
A unique regulatory phase of DNA methylation in the early mammalian embryo
Zachary D. Smith,Michelle Chan,Michelle Chan,Tarjei S. Mikkelsen,Tarjei S. Mikkelsen,Hongcang Gu,Andreas Gnirke,Aviv Regev,Aviv Regev,Alexander Meissner,Alexander Meissner +10 more
TL;DR: The data provide a genome-scale, base-resolution timeline of DNA methylation in the pre-specified embryo, when this epigenetic modification is most dynamic, before returning to the canonical somatic pattern.
References
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Journal ArticleDOI
Conversion of 5-Methylcytosine to 5-Hydroxymethylcytosine in Mammalian DNA by MLL Partner TET1
Mamta Tahiliani,Kian Peng Koh,Yinghua Shen,William A. Pastor,Hozefa S. Bandukwala,Yevgeny Brudno,Suneet Agarwal,Lakshminarayan M. Iyer,David R. Liu,L. Aravind,Anjana Rao +10 more
TL;DR: It is shown here that TET1, a fusion partner of the MLL gene in acute myeloid leukemia, is a 2-oxoglutarate (2OG)- and Fe(II)-dependent enzyme that catalyzes conversion of 5mC to 5-hydroxymethylcytosine (hmC) in cultured cells and in vitro.
Journal ArticleDOI
Human DNA methylomes at base resolution show widespread epigenomic differences
Ryan Lister,Mattia Pelizzola,Robert H. Dowen,R. David Hawkins,Gary C. Hon,Julian Tonti-Filippini,Joseph R. Nery,Leonard Lee,Zhen Ye,Que Minh Ngo,Lee Edsall,Jessica Antosiewicz-Bourget,Jessica Antosiewicz-Bourget,Ron Stewart,Ron Stewart,Victor Ruotti,Victor Ruotti,A. Harvey Millar,James A. Thomson,Bing Ren,Bing Ren,Joseph R. Ecker +21 more
TL;DR: The first genome-wide, single-base-resolution maps of methylated cytosines in a mammalian genome, from both human embryonic stem cells and fetal fibroblasts, along with comparative analysis of messenger RNA and small RNA components of the transcriptome, several histone modifications, and sites of DNA-protein interaction for several key regulatory factors were presented in this article.
Journal ArticleDOI
Genome-wide maps of chromatin state in pluripotent and lineage-committed cells
Tarjei S. Mikkelsen,Manching Ku,Manching Ku,David B. Jaffe,Biju Issac,Biju Issac,Erez Lieberman Aiden,Erez Lieberman Aiden,Georgia Giannoukos,Pablo Alvarez,William Brockman,Tae Kyung Kim,Richard Koche,Richard Koche,Richard Koche,William Lee,Eric M. Mendenhall,Eric M. Mendenhall,Aisling O'Donovan,Aviva Presser,Carsten Russ,Xiaohui Xie,Alexander Meissner,Marius Wernig,Rudolf Jaenisch,Chad Nusbaum,Eric S. Lander,Eric S. Lander,Bradley E. Bernstein,Bradley E. Bernstein +29 more
TL;DR: The application of single-molecule-based sequencing technology for high-throughput profiling of histone modifications in mammalian cells is reported and it is shown that chromatin state can be read in an allele-specific manner by using single nucleotide polymorphisms.
Journal ArticleDOI
The Nuclear DNA Base 5-Hydroxymethylcytosine Is Present in Purkinje Neurons and the Brain
TL;DR: It is shown that, as well as 5mC in mammalian genomes, there are also significant amounts of 5-hydroxymethylcytosine (5hmC) in DNA of Purkinje neurons, which have large nuclei with apparently very little heterochromatin.
Journal ArticleDOI
Integration of External Signaling Pathways with the Core Transcriptional Network in Embryonic Stem Cells
Xi Chen,Han Xu,Ping Yuan,Fang Fang,Fang Fang,Mikael Huss,Vinsensius B. Vega,Eleanor Wong,Yuriy L. Orlov,Weiwei Zhang,Weiwei Zhang,Jianming Jiang,Jianming Jiang,Yuin-Han Loh,Yuin-Han Loh,Hock Chuan Yeo,Zhen Xuan Yeo,Vipin Narang,Kunde R Govindarajan,Bernard Leong,Atif Shahab,Yijun Ruan,Guillaume Bourque,Wing-Kin Sung,Neil D. Clarke,Chia-Lin Wei,Huck-Hui Ng,Huck-Hui Ng +27 more
TL;DR: This study uses chromatin immunoprecipitation coupled with ultra-high-throughput DNA sequencing to map the locations of TF-binding sites and identifies important features of the transcriptional regulatory networks that define ES-cell identity.