Get access

Site-specific human histone H3 methylation stability: fast K4me3 turnover

Authors

  • Yupeng Zheng,

    1. Departments of Chemistry and Molecular Biosciences, Chemistry of Life Processes Institute, Northwestern University, Evanston, IL, USA
    Search for more papers by this author
  • Jeremiah D. Tipton,

    1. Departments of Chemistry and Molecular Biosciences, Chemistry of Life Processes Institute, Northwestern University, Evanston, IL, USA
    Search for more papers by this author
    • Current address: AB Sciex, Tampa, FL, USA

  • Paul M. Thomas,

    1. Departments of Chemistry and Molecular Biosciences, Chemistry of Life Processes Institute, Northwestern University, Evanston, IL, USA
    Search for more papers by this author
  • Neil L. Kelleher,

    1. Departments of Chemistry and Molecular Biosciences, Chemistry of Life Processes Institute, Northwestern University, Evanston, IL, USA
    Search for more papers by this author
  • Steve M. M. Sweet

    Corresponding author
    1. Departments of Chemistry and Molecular Biosciences, Chemistry of Life Processes Institute, Northwestern University, Evanston, IL, USA
    • Correspondence: Dr Steve Sweet, Genome Damage and Stability Centre, University of Sussex, UK

      E-mail: S.M.Sweet@sussex.ac.uk

    Search for more papers by this author

  • Colour Online: See the article online to view Fig. 4 in colour.

Abstract

We employ stable-isotope labeling and quantitative mass spectrometry to track histone methylation stability. We show that H3 trimethyl K9 and K27 are slow to be established on new histones and slow to disappear from old histones, with half-lives of multiple cell divisions. By contrast, the transcription-associated marks K4me3 and K36me3 turn over far more rapidly, with half-lives of 6.8 h and 57 h, respectively. Inhibition of demethylases increases K9 and K36 methylation, with K9 showing the largest and most robust increase. We interpret different turnover rates in light of genome-wide localization data and transcription-dependent nucleosome rearrangements proximal to the transcription start site.

Get access to the full text of this article

Ancillary