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PMID: 23602153 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Genome-wide profiling of 5-formylcytosine reveals its roles in epigenetic priming.

Cell ·Vol. 153 ·No. 3 ·2013-04-25 ·Pages 678-91

Song CX, Szulwach KE, Dai Q, Fu Y, Mao SQ, Lin L, Street C, Li Y, Poidevin M, Wu H, Gao J, Liu P, Li L, Xu GL, Jin P, He C

Abstract

TET proteins oxidize 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC). 5fC and 5caC are excised by mammalian DNA glycosylase TDG, implicating 5mC oxidation in DNA demethylation. Here, we show that the genomic locations of 5fC can be determined by coupling chemical reduction with biotin tagging. Genome-wide mapping of 5fC in mouse embryonic stem cells (mESCs) reveals that 5fC preferentially occurs at poised enhancers among other gene regulatory elements. Application to Tdg null mESCs further suggests that 5fC production coordinates with p300 in remodeling epigenetic states of enhancers. This process, which is not influenced by 5hmC, appears to be associated with further oxidation of 5hmC and commitment to demethylation through 5fC. Finally, we resolved 5fC at base resolution by hydroxylamine-based protection from bisulfite-mediated deamination, thereby confirming sites of 5fC accumulation. Our results reveal roles of active 5mC/5hmC oxidation and TDG-mediated demethylation in epigenetic tuning at regulatory elements.

MeSH Terms
5-Methylcytosine/metabolism Animals Cytosine/analogs & derivatives,metabolism Embryonic Stem Cells/metabolism Epigenesis, Genetic Genetic Techniques Genome-Wide Association Study Mice Regulatory Elements, Transcriptional p300-CBP Transcription Factors/metabolism
Chemicals
5-formylcytosine 5-Methylcytosine Cytosine p300-CBP Transcription Factors
Authors & Affiliations
16 authors, click to expand affiliations / ORCID
Song Chun-Xiao
Department of Chemistry and Institute for Biophysical Dynamics, University of Chicago, Chicago, IL 60637, USA.
Szulwach Keith E
Dai Qing
Fu Ye
Mao Shi-Qing
Lin Li
Street Craig
Li Yujing
Poidevin Mickael
Wu Hao
Gao Juan
Liu Peng
Li Lin
Xu Guo-Liang
Jin Peng
He Chuan
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Article Info
Journal
Cell
Abbr.
Cell
ISSN
1097-4172
DOI
10.1016/j.cell.2013.04.001
Published
2013-04-25
Epub
2013-00-18
Pages
678-91
Language
English
Region
United States
NLM ID
0413066
PMCID
PMC3657391
Subset
IM
Grants
NHGRI NIH HHS · K01 HG006699 · United States
NINDS NIH HHS · NS051630 · United States
NHGRI NIH HHS · HG006827 · United States
NINDS NIH HHS · NS079625 · United States
NHGRI NIH HHS · R01 HG006827 · United States
NINDS NIH HHS · R01 NS079625 · United States
NICHD NIH HHS · HD073162 · United States
NICHD NIH HHS · R21 HD073162 · United States
NIA NIH HHS · AG025688 · United States
NIA NIH HHS · P50 AG025688 · United States
Databases
GEO
GSE41545
Corrections
CommentIn
PMID: 23732041
CommentIn
PMID: 23866334
External Links
PubMed source DOI: 10.1016/j.cell.2013.04.001 PMC Full Text View journal details
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