Long-distance combinatorial linkage between methylation and acetylation on histone H3 N termini

Sean D. Taverna, Beatrix M. Ueberheide, Yifan Liu, Alan J. Tackett, Robert L. Dias, Jeffrey Shabanowitz, Brian T. Chait, Donald F. Hunt, C. David Allis

Research output: Contribution to journalArticlepeer-review


Individual posttranslational modifications (PTMs) on histones have well established roles in certain biological processes, notably transcriptional programming. Recent genomewide studies describe patterns of covalent modifications, such as H3 methylation and acetylation at promoters of specific target genes, or "bivalent domains," in stem cells, suggestive of a possible combinatorial interplay between PTMs on the same histone. However, detection of long-range PTM associations is often problematic in antibody-based or traditional mass spectrometric-based analyses. Here, histone H3 from a ciliate model was analyzed as an enriched source of transcriptionally active chromatin. Using a recently developed mass spectrometric approach, combinatorial modification states on single, long N-ternminal H3 fragments (residues 1-50) were determined. The entire modification status of intact N termini was obtained and indicated correlations between K4 methylation and H3 acetylation. In addition, K4 and K27 methylation were identified concurrently on one H3 species. This methodology is applicable to other histones and larger polypeptides and will likely be a valuable tool in understanding the roles of combinatorial patterns of PTMs.

Original languageEnglish (US)
Pages (from-to)2086-2091
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number7
StatePublished - Feb 13 2007
Externally publishedYes


  • Bivalent domain
  • Electron transfer dissociation
  • Mass spectrometry
  • Posttranslational modifications
  • Tetrahymena

ASJC Scopus subject areas

  • General


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