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Identification of novel histone post-translational modifications by peptide mass fingerprinting

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Abstract

The extent and pattern of histone post-translational modifications is a key determinant dictating the structure of chromatin. We employed mass spectrometry to map the post-translational modifications present on mammalian core histones. Using accurate peptide mass fingerprinting on proteolytic digests of purified histones, we identified more than 20 novel sites of histone modification. One newly identified site of methylation, histone H4 lysine 59, maps to the surface of the nucleosome in close proximity to the site of the only identified histone core modification, histone H3 lysine 79. Consistent with the role of histone H3 lysine 79 methylation in the formation of silent chromatin structure, histone H4 lysine 59 is essential for transcriptional silencing at the yeast silent mating loci and telomeres.

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Fig. 1A–D.
Fig. 2A–D.
Fig. 3.
Fig. 4A, B.

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Acknowledgements

We thank D. Gottschling for yeast strains, C. Bell for assistance with the rendering of crystal structures and A. Sklenar for critical reading of the manuscript. This work was funded by grants from the National Science Foundation (CHE-0089172), the Camille and Henry Dreyfus Foundation and the Ohio State University to M.A.F. and from the American Cancer Society (RPG-00-340-01-CSM) to M.R.P.

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Authors and Affiliations

  1. Department of Chemistry, The Ohio State University, Columbus, OH 43210, USA

    Liwen Zhang & Michael A. Freitas

  2. Department of Molecular and Cellular Biochemistry, The Ohio State University, Columbus, OH 43210, USA

    Ericka E. Eugeni & Mark R. Parthun

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  1. Liwen Zhang
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  2. Ericka E. Eugeni
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  3. Mark R. Parthun
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  4. Michael A. Freitas
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Correspondence to Michael A. Freitas.

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Edited by: B. McKee

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Zhang, L., Eugeni, E.E., Parthun, M.R. et al. Identification of novel histone post-translational modifications by peptide mass fingerprinting. Chromosoma 112, 77–86 (2003). https://doi.org/10.1007/s00412-003-0244-6

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  • DOI: https://doi.org/10.1007/s00412-003-0244-6

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