Genome-wide Profiling of 5-Formylcytosine Reveals Its Roles in Epigenetic Priming | Zendy

ChunXiao Song | Zendy; Keith E. Szulwach | Zendy; Qing Dai | Zendy; Ye Fu | Zendy; Shi-Qing Mao | Zendy; Li Lin | Zendy; Craig Street | Zendy; Yujing Li | Zendy; Mickaël Poidevin | Zendy; Hao Wu | Zendy; Juan Gao | Zendy; Peng Liu | Zendy; Guoliang Xu | Zendy; Peng Jin | Zendy; Chuan He | Zendy

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Genome-wide Profiling of 5-Formylcytosine Reveals Its Roles in Epigenetic Priming

Author(s) -

ChunXiao Song,

Keith E. Szulwach,

Qing Dai,

Ye Fu,

Shi-Qing Mao,

Li Lin,

Craig Street,

Yujing Li,

Mickaël Poidevin,

Hao Wu,

Juan Gao,

Peng Liu,

Guoliang Xu,

Peng Jin,

Chuan He

Publication year - 2013

Publication title -

cell

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 26.304

H-Index - 776

eISSN - 1097-4172

pISSN - 0092-8674

DOI - 10.1016/j.cell.2013.04.001

Subject(s) - 5 hydroxymethylcytosine , biology , dna demethylation , 5 methylcytosine , epigenetics , enhancer , demethylation , dna , dna methylation , microbiology and biotechnology , gene , genetics , biochemistry , gene expression

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.

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