Phosphorylation of histone H3 Ser10 establishes a hierarchy for subsequent intramolecular modification events

Stamatios Liokatis; Alexandra Stützer; Simon J. Elsässer; Francois Xavier Theillet; Rebecca Klingberg; Barth Van Rossum; Dirk Schwarzer; C. David Allis; Wolfgang Fischle; Philipp Selenko

doi:10.1038/nsmb.2310

Phosphorylation of histone H3 Ser10 establishes a hierarchy for subsequent intramolecular modification events

Stamatios Liokatis, Alexandra Stützer, Simon J. Elsässer, Francois Xavier Theillet, Rebecca Klingberg, Barth Van Rossum, Dirk Schwarzer, C. David Allis, Wolfgang Fischle, Philipp Selenko^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

77 Scopus citations

Abstract

Phosphorylation of Ser10 of histone H3 regulates chromosome condensation and transcriptional activity. Using time-resolved, high-resolution NMR spectroscopy, we demonstrate that histone H3 Ser10 phosphorylation inhibits checkpoint kinase 1 (Chk1)-and protein kinase C (PKC)-mediated modification of Thr11 and Thr6, the respective primary substrate sites of these kinases. On unmodified H3, both enzymes also target Ser10 and thereby establish autoinhibitory feedback states on individual H3 tails. Whereas phosphorylated Ser10 does not affect acetylation of Lys14 by Gcn5, phosphorylated Thr11 impedes acetylation. Our observations reveal mechanistic hierarchies of H3 phosphorylation and acetylation events and provide a framework for intramolecular modification cross-talk within the N terminus of histone H3.

Original language	English (US)
Pages (from-to)	819-823
Number of pages	5
Journal	Nature Structural and Molecular Biology
Volume	19
Issue number	8
DOIs	https://doi.org/10.1038/nsmb.2310
State	Published - Aug 2012
Externally published	Yes

Bibliographical note

Funding Information:
We thank P. Schmieder and M. Beerbaum for excellent NMR infrastructure maintenance. A.S. and W.F. acknowledge funding by the Max Planck Gesellschaft (MBG). S.J.E. was supported by a Boehringer Ingelheim Fund (BIF) fellowship. F.-X.T. acknowledges support from the Association pour la Recherche contre le Cancer (ARC). D.S. and P.S. are supported by Emmy Noether research grants (SCHW1163/3-1 and SE1794/1-1) from the Deutsche Forschungsgemeinschaft (DFG).

ASJC Scopus subject areas

Structural Biology
Molecular Biology

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title = "Phosphorylation of histone H3 Ser10 establishes a hierarchy for subsequent intramolecular modification events",

abstract = "Phosphorylation of Ser10 of histone H3 regulates chromosome condensation and transcriptional activity. Using time-resolved, high-resolution NMR spectroscopy, we demonstrate that histone H3 Ser10 phosphorylation inhibits checkpoint kinase 1 (Chk1)-and protein kinase C (PKC)-mediated modification of Thr11 and Thr6, the respective primary substrate sites of these kinases. On unmodified H3, both enzymes also target Ser10 and thereby establish autoinhibitory feedback states on individual H3 tails. Whereas phosphorylated Ser10 does not affect acetylation of Lys14 by Gcn5, phosphorylated Thr11 impedes acetylation. Our observations reveal mechanistic hierarchies of H3 phosphorylation and acetylation events and provide a framework for intramolecular modification cross-talk within the N terminus of histone H3.",

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note = "Funding Information: We thank P. Schmieder and M. Beerbaum for excellent NMR infrastructure maintenance. A.S. and W.F. acknowledge funding by the Max Planck Gesellschaft (MBG). S.J.E. was supported by a Boehringer Ingelheim Fund (BIF) fellowship. F.-X.T. acknowledges support from the Association pour la Recherche contre le Cancer (ARC). D.S. and P.S. are supported by Emmy Noether research grants (SCHW1163/3-1 and SE1794/1-1) from the Deutsche Forschungsgemeinschaft (DFG).",

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AU - Liokatis, Stamatios

AU - Stützer, Alexandra

AU - Elsässer, Simon J.

AU - Theillet, Francois Xavier

AU - Klingberg, Rebecca

AU - Van Rossum, Barth

AU - Schwarzer, Dirk

AU - Allis, C. David

AU - Fischle, Wolfgang

AU - Selenko, Philipp

N1 - Funding Information: We thank P. Schmieder and M. Beerbaum for excellent NMR infrastructure maintenance. A.S. and W.F. acknowledge funding by the Max Planck Gesellschaft (MBG). S.J.E. was supported by a Boehringer Ingelheim Fund (BIF) fellowship. F.-X.T. acknowledges support from the Association pour la Recherche contre le Cancer (ARC). D.S. and P.S. are supported by Emmy Noether research grants (SCHW1163/3-1 and SE1794/1-1) from the Deutsche Forschungsgemeinschaft (DFG).

PY - 2012/8

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N2 - Phosphorylation of Ser10 of histone H3 regulates chromosome condensation and transcriptional activity. Using time-resolved, high-resolution NMR spectroscopy, we demonstrate that histone H3 Ser10 phosphorylation inhibits checkpoint kinase 1 (Chk1)-and protein kinase C (PKC)-mediated modification of Thr11 and Thr6, the respective primary substrate sites of these kinases. On unmodified H3, both enzymes also target Ser10 and thereby establish autoinhibitory feedback states on individual H3 tails. Whereas phosphorylated Ser10 does not affect acetylation of Lys14 by Gcn5, phosphorylated Thr11 impedes acetylation. Our observations reveal mechanistic hierarchies of H3 phosphorylation and acetylation events and provide a framework for intramolecular modification cross-talk within the N terminus of histone H3.

AB - Phosphorylation of Ser10 of histone H3 regulates chromosome condensation and transcriptional activity. Using time-resolved, high-resolution NMR spectroscopy, we demonstrate that histone H3 Ser10 phosphorylation inhibits checkpoint kinase 1 (Chk1)-and protein kinase C (PKC)-mediated modification of Thr11 and Thr6, the respective primary substrate sites of these kinases. On unmodified H3, both enzymes also target Ser10 and thereby establish autoinhibitory feedback states on individual H3 tails. Whereas phosphorylated Ser10 does not affect acetylation of Lys14 by Gcn5, phosphorylated Thr11 impedes acetylation. Our observations reveal mechanistic hierarchies of H3 phosphorylation and acetylation events and provide a framework for intramolecular modification cross-talk within the N terminus of histone H3.

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Phosphorylation of histone H3 Ser10 establishes a hierarchy for subsequent intramolecular modification events

Abstract

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