Precision mapping of coexisting modifications in histone H3 tails from embryonic stem cells by ETD-MS/MS

Hye Ryung Jung, Simone Sidoli, Simon Haldbo, Richard R. Sprenger, Veit Schwämmle, Diego Pasini, Kristian Helin, Ole N. Jensen

Research output: Contribution to journalArticle

Abstract

Post-translational modifications (PTMs) of histones play a major role in regulating chromatin dynamics and influence processes such as transcription and DNA replication. Here, we report 114 distinct combinations of coexisting PTMs of histone H3 obtained from mouse embryonic stem (ES) cells. Histone H3 N-terminal tail peptides (amino acids 1-50, 5-6 kDa) were separated by optimized weak cation exchange/hydrophilic interaction liquid chromatography (WCX/HILIC) and sequenced online by electron transfer dissociation (ETD) tandem mass spectrometry (MS/MS). High mass accuracy and near complete sequence coverage allowed unambiguous mapping of the major histone marks and discrimination between isobaric and nearly isobaric PTMs such as trimethylation and acetylation. Hierarchical data analysis identified H3K27me2-H3K36me2 as the most frequently observed PTMs in H3. Modifications at H3 residues K27 and K36 often coexist with the abundant mark K23ac, and we identified two frequently occurring quadruplet marks 'K9me1K23acK27me2K36me2' and 'K9me3K23acK27me2K36me', which might indicate a role in crosstalk. Co-occurrence frequency analysis revealed also an interplay between methylations of K9, K27, and K36, suggesting interdependence between histone methylation marks. We hypothesize that the most abundant coexisting PTMs may provide a signature for the permissive state of mouse ES cells.

Original languageEnglish
Pages (from-to)8232-8239
Number of pages8
JournalAnalytical Chemistry
Volume85
Issue number17
DOIs
Publication statusPublished - 2013

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Stem cells
Histones
Electrons
Methylation
Acetylation
Exchange interactions
Liquid chromatography
Transcription
Crosstalk
Chromatin
Mass spectrometry
Cations
Amino Acids
Peptides
DNA

ASJC Scopus subject areas

  • Analytical Chemistry

Cite this

Jung, H. R., Sidoli, S., Haldbo, S., Sprenger, R. R., Schwämmle, V., Pasini, D., ... Jensen, O. N. (2013). Precision mapping of coexisting modifications in histone H3 tails from embryonic stem cells by ETD-MS/MS. Analytical Chemistry, 85(17), 8232-8239. https://doi.org/10.1021/ac401299w

Precision mapping of coexisting modifications in histone H3 tails from embryonic stem cells by ETD-MS/MS. / Jung, Hye Ryung; Sidoli, Simone; Haldbo, Simon; Sprenger, Richard R.; Schwämmle, Veit; Pasini, Diego; Helin, Kristian; Jensen, Ole N.

In: Analytical Chemistry, Vol. 85, No. 17, 2013, p. 8232-8239.

Research output: Contribution to journalArticle

Jung, HR, Sidoli, S, Haldbo, S, Sprenger, RR, Schwämmle, V, Pasini, D, Helin, K & Jensen, ON 2013, 'Precision mapping of coexisting modifications in histone H3 tails from embryonic stem cells by ETD-MS/MS', Analytical Chemistry, vol. 85, no. 17, pp. 8232-8239. https://doi.org/10.1021/ac401299w
Jung, Hye Ryung ; Sidoli, Simone ; Haldbo, Simon ; Sprenger, Richard R. ; Schwämmle, Veit ; Pasini, Diego ; Helin, Kristian ; Jensen, Ole N. / Precision mapping of coexisting modifications in histone H3 tails from embryonic stem cells by ETD-MS/MS. In: Analytical Chemistry. 2013 ; Vol. 85, No. 17. pp. 8232-8239.
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