Access

You are not currently logged in.

Access your personal account or get JSTOR access through your library or other institution:

login

Log in to your personal account or through your institution.

If You Use a Screen Reader

This content is available through Read Online (Free) program, which relies on page scans. Since scans are not currently available to screen readers, please contact JSTOR User Support for access. We'll provide a PDF copy for your screen reader.

N-Formylation of Lysine in Histone Proteins as a Secondary Modification Arising from Oxidative DNA Damage

Tao Jiang, Xinfeng Zhou, Koli Taghizadeh, Min Dong and Peter C. Dedon
Proceedings of the National Academy of Sciences of the United States of America
Vol. 104, No. 1 (Jan. 2, 2007), pp. 60-65
Stable URL: http://www.jstor.org/stable/25426050
Page Count: 6
  • Read Online (Free)
  • Subscribe ($19.50)
  • Cite this Item
Since scans are not currently available to screen readers, please contact JSTOR User Support for access. We'll provide a PDF copy for your screen reader.
N-Formylation of Lysine in Histone Proteins as a Secondary Modification Arising from Oxidative DNA Damage
Preview not available

Abstract

The posttranslational modification of histone and other chromatin proteins has a well recognized but poorly defined role in the physiology of gene expression. With implications for interfering with these epigenetic mechanisms, we now report the existence of a relatively abundant secondary modification of chromatin proteins, the N⁶-formylation of lysine that appears to be uniquely associated with histone and other nuclear proteins. Using both radiolabeling and sensitive bioanalytical methods, we demonstrate that the formyl moiety of 3′-formylphosphate residues arising from 5′-oxidation of deoxyribose in DNA, caused by the enediyne neocarzinostatin, for example, acylate the N⁶-amino groups of lysine side chains. A liquid chromatography (LC)-tandem mass spectrometry (MS) method was developed to quantify the resulting N⁶-formyl-lysine residues, which were observed to be present in unperturbed cells and all sources of histone proteins to the extent of 0.04-0.1% of all lysines in acid-soluble chromatin proteins including histones. Cells treated with neocarzinostatin showed a clear dose-response relationship for the formation of N⁶-formyl-lysine, with this nucleosome linker-selective DNA-cleaving agent causing selective N⁶-formylation of the linker histone H1. The N⁶-formyl-lysine residue appears to represent an endogenous histone secondary modification, one that bears chemical similarity to lysine N⁶-acetylation recognized as an important determinant of gene expression in mammalian cells. The N⁶-formyl modification of lysine may interfere with the signaling functions of lysine acetylation and methylation and thus contribute to the pathophysiology of oxidative and nitrosative stress.

Page Thumbnails

  • Thumbnail: Page 
[60]
    [60]
  • Thumbnail: Page 
61
    61
  • Thumbnail: Page 
62
    62
  • Thumbnail: Page 
63
    63
  • Thumbnail: Page 
64
    64
  • Thumbnail: Page 
65
    65