Dynamic Readers for 5-(Hydroxy)Methylcytosine and Its Oxidized Derivatives

被引：755

作者：

Spruijt, Cornelia G. ^{[1
]}

Gnerlich, Felix ^{[2
]}

Smits, Arne H. ^{[1
]}

Pfaffeneder, Toni ^{[2
]}

Jansen, Pascal W. T. C. ^{[1
]}

Bauer, Christina ^{[3
]}

Muenzel, Martin ^{[2
]}

Wagner, Mirko ^{[2
]}

Mueller, Markus ^{[2
]}

Khan, Fariha ^{[4
,5
]}

Eberl, H. Christian ^{[6
]}

Mensinga, Anneloes ^{[1
]}

Brinkman, Arie B. ^{[7
]}

Lephikov, Konstantin ^{[8
]}

Mueller, Udo ^{[3
]}

Walter, Joern ^{[8
]}

Boelens, Rolf ^{[5
]}

van Ingen, Hugo ^{[5
]}

Leonhardt, Heinrich ^{[3
]}

Carell, Thomas ^{[2
]}

Vermeulen, Michiel ^{[1
]}

机构：

[1] UMC Utrecht, Dept Mol Canc Res Prote & Chromatin Biol, NL-3584 CG Utrecht, Netherlands

[2] Univ Munich, Fak Chem & Pharm, Ctr Integrated Prot Sci, D-81377 Munich, Germany

[3] Univ Munich, Fak Biol, Ctr Integrated Prot Sci, D-82152 Planegg Martinsried, Germany

[4] Pir Mehr Ali Shah Arid Agr Univ Rawalpindi, Univ Inst Biochem & Biotechnol, Rawalpindi, Pakistan

[5] Univ Utrecht, Bijvoet Ctr Biomol Res, NMR Spect Res Grp, NL-3584 CH Utrecht, Netherlands

[6] Max Planck Inst Biochem, D-82152 Martinsried, Germany

[7] Radboud Univ Nijmegen, Nijmegen Ctr Mol Life Sci, Dept Mol Biol, NL-6525 GA Nijmegen, Netherlands

[8] Univ Saarland, D-66123 Saarbrucken, Germany

来源：

CELL | 2013年 / 152卷 / 05期

关键词：

EMBRYONIC STEM-CELLS; HEMI-METHYLATED DNA; ONCOMETABOLITE; 2-HYDROXYGLUTARATE; INTERACTION PROTEOMICS; MAMMALIAN DNA; PROTEIN; 5-HYDROXYMETHYLCYTOSINE; 5-METHYLCYTOSINE; QUANTIFICATION; CHROMATIN;

D O I：

10.1016/j.cell.2013.02.004

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：1146 / 1159

页数：14

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