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Cell. 2013 Feb 28;152(5):1146-59. doi: 10.1016/j.cell.2013.02.004. Epub 2013 Feb 21.

Dynamic readers for 5-(hydroxy)methylcytosine and its oxidized derivatives.

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1
Department of Molecular Cancer Research, Proteomics and Chromatin Biology, UMC Utrecht, 3584 CG Utrecht, the Netherlands.

Abstract

Tet proteins oxidize 5-methylcytosine (mC) to generate 5-hydroxymethyl (hmC), 5-formyl (fC), and 5-carboxylcytosine (caC). The exact function of these oxidative cytosine bases remains elusive. We applied quantitative mass-spectrometry-based proteomics to identify readers for mC and hmC in mouse embryonic stem cells (mESC), neuronal progenitor cells (NPC), and adult mouse brain tissue. Readers for these modifications are only partially overlapping, and some readers, such as Rfx proteins, display strong specificity. Interactions are dynamic during differentiation, as for example evidenced by the mESC-specific binding of Klf4 to mC and the NPC-specific binding of Uhrf2 to hmC, suggesting specific biological roles for mC and hmC. Oxidized derivatives of mC recruit distinct transcription regulators as well as a large number of DNA repair proteins in mouse ES cells, implicating the DNA damage response as a major player in active DNA demethylation.

PMID:
23434322
DOI:
10.1016/j.cell.2013.02.004
[Indexed for MEDLINE]
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