Global assessment of combinatorial post-translational modification of core histones in yeast using contemporary mass spectrometry: LYS4 trimethylation correlates with degree of acetylation on the same H3 tail

Lihua Jiang, Jonell N. Smith, Shannon L. Anderson, Ping Ma, Craig A. Mizzen, Neil L. Kelleher*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

73 Scopus citations

Abstract

A global view of all core histones in yeast is provided by tandem mass spectrometry of intact histones H2A, H2B, H4, and H3. This allowed detailed characterization of >50 distinct histone forms and their semiquantitative assessment in the deletion mutants gcn5Δ, spt7Δ, ahc1Δ, and rtg2Δ, affecting the chromatin remodeling complexes SAGA, SLIK, and ADA. The "top down" mass spectrometry approach detected dramatic decreases in acetylation on H3 and H2B in gcn5Δ cells versus wild type. For H3 in wild type cells, tandem mass spectrometry revealed a direct correlation between increases of Lys4 trimethylation and the 0, 1, 2, and 3 acetylation states of histone H3. The results show a wide swing from 10 to 80% Lys 4 trimethylation levels on those H3 tails harboring 0 or 3 acetylations, respectively. Reciprocity between these chromatin marks was apparent, since gcn5Δ cells showed a 30% decrease in trimethylation levels on Lys4 in addition to a decrease of acetylation levels on H3 in bulk chromatin. Deletion of Set1, the Lys4 methyltransferase, was associated with the linked disappearance of both Lys4 methylation and Lys14 and Lys18 or Lys23 acetylation on H3. In sum, we have defined the "basis set" of histone forms present in yeast chromatin using a current mass spectrometric approach that both quickly profiles global changes and directly probes the connectivity of modifications on the same histone.

Original languageEnglish (US)
Pages (from-to)27923-27934
Number of pages12
JournalJournal of Biological Chemistry
Volume282
Issue number38
DOIs
StatePublished - Sep 21 2007

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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