title: Cis-existence of H3K27me3 and H3K36me2 in mouse embryonic stem cells revealed by specific ions of isobaric modification chromatogram.
abstract: BACKGROUND
  Histone H3 lysine 27 trimethylation (H3K27me3) and H3 lysine 36 trimethylation (H3K36me3) are important epigenetic modifications correlated with transcription repression and activation, respectively. These two opposing modifications rarely co-exist in the same H3 polypeptide. However, a small but significant amount of H3 tails are modified with 5 methyl groups on K27 and K36 in mouse embryonic stem cells (mESCs) and it is unclear how the trimethylation is distributed on K27 or K36.
  
  
  METHODS
  A label-free, bottom-up mass spectrum method, named specific ions of isobaric modification chromatogram (SIMC), was established to quantify the relative abundance of K27me2-K36me3 and K27me3-K36me2 in the same histone H3 tail.
  
  
  RESULTS
  By using this method, we demonstrated that the H3K27me3-K36me2 comprises about 85 % of the penta-methylated H3 tails at K27 and K36 in mESCs. Upon mESC differentiation, the abundance of H3K27me3-K36me2 significantly decreased, while the level of H3K27me2-K36me3 remains unchanged.
  
  
  CONCLUSIONS
  Our study not only revealed the cis-existence of H3K27me3-K36me2 in mESCs, but also suggested that this combinatorial histone modification may assume a specific regulatory function during differentiation.
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China. mao.hailei@zs-hospital.sh.cn.|State Key Laboratory of Molecular Biology, and Shanghai Key laboratory of Molecular Andrology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai, 200031, China. mao.hailei@zs-hospital.sh.cn.
authors.forename: Hailei
authors.initials: H
authors.lastname: Mao
authors.affiliation: State Key Laboratory of Molecular Biology, and Shanghai Key laboratory of Molecular Andrology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai, 200031, China. ghan@sibcb.ac.cn.
authors.forename: Gang
authors.initials: G
authors.lastname: Han
authors.affiliation: State Key Laboratory of Molecular Biology, and Shanghai Key laboratory of Molecular Andrology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai, 200031, China. xulongyong@sibcb.ac.cn.
authors.forename: Longyong
authors.initials: L
authors.lastname: Xu
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China. zhu.duming@zs-hospital.sh.cn.
authors.forename: Duming
authors.initials: D
authors.lastname: Zhu
authors.affiliation: State Key Laboratory of Molecular Biology, and Shanghai Key laboratory of Molecular Andrology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai, 200031, China. hqlin@sibcb.ac.cn.
authors.forename: Hanqing
authors.initials: H
authors.lastname: Lin
authors.affiliation: State Key Laboratory of Molecular Biology, and Shanghai Key laboratory of Molecular Andrology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai, 200031, China. caoxw@sibcb.ac.cn.
authors.forename: Xiongwen
authors.initials: X
authors.lastname: Cao
authors.affiliation: State Key Laboratory of Molecular Biology, and Shanghai Key laboratory of Molecular Andrology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai, 200031, China. yuyi@sibcb.ac.cn.
authors.forename: Yi
authors.initials: Y
authors.lastname: Yu
authors.affiliation: State Key Laboratory of Molecular Biology, and Shanghai Key laboratory of Molecular Andrology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai, 200031, China. cdchen@sibcb.ac.cn.
authors.forename: Charlie Degui
authors.initials: CD
authors.lastname: Chen
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D006657:Histones / Q000378:metabolism*; D051379:Mice; D000066450:Mouse Embryonic Stem Cells / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism; D053719:Tandem Mass Spectrometry
chemical_list: D006657:Histones; D010455:Peptides