Quantitative proteomic analysis of post-translational modifications of human histones - PubMed

Affiliations

• PMID: 16627869
• DOI: 10.1074/mcp.M600007-MCP200

Free article

Comparative Study

Quantitative proteomic analysis of post-translational modifications of human histones

Hans Christian Beck et al. Mol Cell Proteomics. 2006 Jul.

Free article

Abstract

Histone proteins are subject to a range of post-transcriptional modifications in living cells. The combinatorial nature of these modifications constitutes the "histone code" that dictates chromatin structure and function during development, growth, differentiation, and homeostasis of cells. Deciphering of the histone code is hampered by the lack of analytical methods for monitoring the combinatorial complexity of reversible multisite modifications of histones, including acetylation and methylation. To address this problem, we used LC-MSMS technology and Virtual Expert Mass Spectrometrist software for qualitative and quantitative proteomic analysis of histones extracted from human small cell lung cancer cells. A total of 32 acetylations, methylations, and ubiquitinations were located in the human histones H2A, H2B, H3, and H4, including seven novel modifications. An LC-MSMS-based method was applied in a quantitative proteomic study of the dose-response effect of the histone deacetylase inhibitor (HDACi) PXD101 on histone acetylation in human cell cultures. Triplicate LC-MSMS runs at six different HDACi concentrations demonstrated that PXD101 affects acetylation of histones H2A, H2B, H3, and H4 in a site-specific and dose-dependent manner. This unbiased analysis revealed that a relative increase in acetylated peptide from the histone variants H2A, H2B, and H4 was accompanied by a relative decrease of dimethylated Lys(57) from histone H2B. The dose-response results obtained by quantitative proteomics of histones from HDACi-treated cells were consistent with Western blot analysis of histone acetylation, cytotoxicity, and dose-dependent expression profiles of p21 and cyclin A2. This demonstrates that mass spectrometry-based quantitative proteomic analysis of post-translational modifications is a viable approach for functional analysis of candidate drugs, such as HDAC inhibitors.

Similar articles

• Quantification of SAHA-Dependent Changes in Histone Modifications Using Data-Independent Acquisition Mass Spectrometry.

  Krautkramer KA, Reiter L, Denu JM, Dowell JA. Krautkramer KA, et al. J Proteome Res. 2015 Aug 7;14(8):3252-62. doi: 10.1021/acs.jproteome.5b00245. Epub 2015 Jul 13. J Proteome Res. 2015. PMID: 26120868 Free PMC article.

• Mass spectrometry and DigiWest technology emphasize protein acetylation profile from Quisinostat-treated HuT78 CTCL cell line.

  Méhul B, Perrin A, Grisendi K, Galindo AN, Dayon L, Ménigot C, Rival Y, Voegel JJ. Méhul B, et al. J Proteomics. 2018 Sep 15;187:126-143. doi: 10.1016/j.jprot.2018.07.003. Epub 2018 Jul 18. J Proteomics. 2018. PMID: 30012418

• The role of histone H2A and H2B post-translational modifications in transcription: a genomic perspective.

  Wyrick JJ, Parra MA. Wyrick JJ, et al. Biochim Biophys Acta. 2009 Jan;1789(1):37-44. doi: 10.1016/j.bbagrm.2008.07.001. Epub 2008 Jul 14. Biochim Biophys Acta. 2009. PMID: 18675384 Review.

• Integrative Chemical Biology Approaches to Deciphering the Histone Code: A Problem-Driven Journey.

  Li X, Li XD. Li X, et al. Acc Chem Res. 2021 Oct 5;54(19):3734-3747. doi: 10.1021/acs.accounts.1c00463. Epub 2021 Sep 23. Acc Chem Res. 2021. PMID: 34553920 Review.

Cited by

• Histone Tail Cleavage as a Mechanism for Epigenetic Regulation.

  Shin Y. Shin Y. Int J Mol Sci. 2024 Oct 8;25(19):10789. doi: 10.3390/ijms251910789. Int J Mol Sci. 2024. PMID: 39409117 Free PMC article. Review.

• Transfer-messenger RNA controls the translation of cell-cycle and stress proteins in Streptomyces.

  Barends S, Zehl M, Bialek S, de Waal E, Traag BA, Willemse J, Jensen ON, Vijgenboom E, van Wezel GP. Barends S, et al. EMBO Rep. 2010 Feb;11(2):119-25. doi: 10.1038/embor.2009.255. Epub 2009 Dec 18. EMBO Rep. 2010. PMID: 20019758 Free PMC article.

• Large scale analysis of co-existing post-translational modifications in histone tails reveals global fine structure of cross-talk.

  Schwämmle V, Aspalter CM, Sidoli S, Jensen ON. Schwämmle V, et al. Mol Cell Proteomics. 2014 Jul;13(7):1855-65. doi: 10.1074/mcp.O113.036335. Epub 2014 Apr 16. Mol Cell Proteomics. 2014. PMID: 24741113 Free PMC article.

• Trimethylacetic Anhydride-Based Derivatization Facilitates Quantification of Histone Marks at the MS1 Level.

  Kuchaříková H, Dobrovolná P, Lochmanová G, Zdráhal Z. Kuchaříková H, et al. Mol Cell Proteomics. 2021;20:100114. doi: 10.1016/j.mcpro.2021.100114. Epub 2021 Jun 12. Mol Cell Proteomics. 2021. PMID: 34129942 Free PMC article.

Publication types

MeSH terms

Substances

LinkOut - more resources

• Full Text Sources

  • Elsevier Science

• Other Literature Sources

  • The Lens - Patent Citations Database

• Molecular Biology Databases

  • GlyGen glycoinformatics resource
  • PhosphoSitePlus