title: Dynamic readers for 5-(hydroxy)methylcytosine and its oxidized derivatives.
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.
authors: Department of Molecular Cancer Research, Proteomics and Chromatin Biology, UMC Utrecht, 3584 CG Utrecht, the Netherlands.
authors: Cornelia G
authors: CG
authors: Spruijt
authors: Felix
authors: F
authors: Gnerlich
authors: Arne H
authors: AH
authors: Smits
authors: Toni
authors: T
authors: Pfaffeneder
authors: Pascal W T C
authors: PW
authors: Jansen
authors: Christina
authors: C
authors: Bauer
authors: Martin
authors: M
authors: Münzel
authors: Mirko
authors: M
authors: Wagner
authors: Markus
authors: M
authors: Müller
authors: Fariha
authors: F
authors: Khan
authors: H Christian
authors: HC
authors: Eberl
authors: Anneloes
authors: A
authors: Mensinga
authors: Arie B
authors: AB
authors: Brinkman
authors: Konstantin
authors: K
authors: Lephikov
authors: Udo
authors: U
authors: Müller
authors: Jörn
authors: J
authors: Walter
authors: Rolf
authors: R
authors: Boelens
authors: Hugo
authors: H
authors: van Ingen
authors: Heinrich
authors: H
authors: Leonhardt
authors: Thomas
authors: T
authors: Carell
authors: Michiel
authors: M
authors: Vermeulen
mesh_terms: D044503:5-Methylcytosine / Q000032:analysis* / Q000378:metabolism / Q000031:analogs & derivatives; D000818:Animals; D001921:Brain / Q000166:cytology / Q000378:metabolism; D003596:Cytosine / Q000031:analogs & derivatives* / Q000032:analysis / Q000378:metabolism; D045647:DNA Glycosylases / Q000378:metabolism; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000378:metabolism; D000090062:Kruppel-Like Factor 4; D013058:Mass Spectrometry; D051379:Mice; D010084:Oxidation-Reduction; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D000071701:Regulatory Factor X Transcription Factors; D013234:Stem Cells / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; C000715468:Klf4 protein, mouse; D000090062:Kruppel-Like Factor 4; D011518:Proto-Oncogene Proteins; C509133:RFX5 protein, mouse; D000071701:Regulatory Factor X Transcription Factors; C540839:TET1 protein, mouse; D014157:Transcription Factors; C011865:5-hydroxymethylcytosine; D044503:5-Methylcytosine; D003596:Cytosine; C571025:UHRF2 protein, mouse; D044767:Ubiquitin-Protein Ligases; D045647:DNA Glycosylases