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Chemical probes for histone-modifying enzymes

Nature Chemical Biology volume 4, pages 590–597 (2008)Cite this article

Abstract

The histone-modifying enzymes that catalyze reversible lysine acetylation and methylation are central to the epigenetic regulation of chromatin remodeling. From the early discovery of histone deacetylase inhibitors to the more recent identification of histone demethylase blockers, chemical approaches offer increasingly sophisticated tools for the investigation of the structure and function of these lysine-modifying enzymes. This review summarizes progress to date on compounds identified from screens or by design that can modulate the activity of classical histone deacetylases, sirtuins, histone acetyltransferases, histone methyltransferases and histone demethylases. We highlight applications of compounds to mechanistic and functional studies involving these enzymes and discuss future challenges regarding target specificity and general utility.

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Figure 1: Reversible histone acetylation catalyzed by histone acetyltransferases, classical histone deacetylases and sirtuins.
Figure 2: Reversible histone methylation catalyzed by histone methyltransferases, LSD1 demethylase and Jmj demethylases.
Figure 3: Selected classical histone deacetylase inhibitors.
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Acknowledgements

I am grateful to members of my group past and present, as well as many collaborators in this field for many helpful discussions and for their key roles in the work cited. I also thank the US National Institutes of Health, the Flight Attendant Medical Research Institute and the Kaufman Foundation for support.

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    Philip A Cole

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Cole, P. Chemical probes for histone-modifying enzymes. Nat Chem Biol 4, 590–597 (2008). https://doi.org/10.1038/nchembio.111

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