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

Spruijt, C. G., Gnerlich, F., Smits, A. H., Pfaffeneder, T., Jansen, P. W. T. C., Bauer, C., et al. (2013). Dynamic Readers for 5-(Hydroxy)Methylcytosine and Its Oxidized Derivatives. CELL, 152(5), 1146-1159. doi:10.1016/j.cell.2013.02.004.

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 Creators:
Spruijt, Cornelia G.1, Author
Gnerlich, Felix1, Author
Smits, Arne H.1, Author
Pfaffeneder, Toni1, Author
Jansen, Pascal W. T. C.1, Author
Bauer, Christina1, Author
Muenzel, Martin1, Author
Wagner, Mirko1, Author
Mueller, Markus1, Author
Khan, Fariha1, Author
Eberl, Hans Christian2, Author           
Mensinga, Anneloes1, Author
Brinkman, Arie B.1, Author
Lephikov, Konstantin1, Author
Mueller, Udo1, Author
Walter, Joern1, Author
Boelens, Rolf1, Author
van Ingen, Hugo1, Author
Leonhardt, Heinrich1, Author
Carell, Thomas1, Author
Vermeulen, Michiel1, Author more..
Affiliations:
1external, ou_persistent22              
2Mann, Matthias / Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565159              

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

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Language(s): eng - English
 Dates: 2013-02-08
 Publication Status: Issued
 Pages: 14
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Degree: -

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Title: CELL
Source Genre: Journal
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Publ. Info: 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA : CELL PRESS
Pages: - Volume / Issue: 152 (5) Sequence Number: - Start / End Page: 1146 - 1159 Identifier: ISSN: 0092-8674