Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2008 Oct;4(10):590-7.
doi: 10.1038/nchembio.111.

Chemical probes for histone-modifying enzymes

Philip A Cole  1
Affiliations
Review

Chemical probes for histone-modifying enzymes

Philip A Cole. Nat Chem Biol. 2008 Oct.

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.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Reversible histone acetylation catalyzed by histone acetyltransferases (HATs), classical histone deacetylases (HDACs), and sirtuins (Sir2s). Transferred acetyl group is highlighted in blue. R = 3',5'-adenosine diphosphate; R1 = adenosine 5'-diphosphate.
Figure 2
Figure 2
Reversible histone methylation catalyzed by histone methyltransferases, LSD1 demethylase, and Jmj demethylases. Transferred methyl group highlighted in red. R = methyl or hydrogen; R1 = ribose-adenosine 5'-diphosphosphate.
Figure 3
Figure 3
Selected classical histone deacetylase inhibitors. Warhead features highlighted in red.
Figure 4
Figure 4
Activators and inhibitors of Sir2 enzymes.
Figure 5
Figure 5
Natural product and synthetic histone acetyltransferase inhibitors.
Fig. 6
Fig. 6
Histone methyltransferase inhibitors.
Figure 7
Figure 7
Histone demethylase inhibitors.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Goldberg AD, Allis CD, Bernstein E. Epigenetics: a landscape takes shape. Cell. 2007;128:635–638. - PubMed
    1. Taverna SD, Li H, Ruthenburg AJ, Allis CD, Patel DJ. How chromatin-binding modules interpret histone modifications. Nat. Struct. Mol. Biol. 2007;14:1025–1040. - PMC - PubMed
    1. Allfrey VG, Faulkner R, Mirsky AE. Acetylation and methylation of histones and their possible role in the regulation of RNA synthesis. Proc. Natl. Acad. Sci. USA. 1964;51:786–794. - PMC - PubMed
    1. Murray K. The occurrence of ε-N-methyl lysine in histones. Biochemistry. 1964;3:10–15. - PubMed
    1. Gershey EL, Vidali G, Allfrey VG. Chemical studies of histone acetylation. The occurrence of ε-N-acetyllysine in the f2a1 histone. J. Biol. Chem. 1968;243:5018–5022. - PubMed

Publication types

MeSH terms

LinkOut - more resources

  NODES
twitter 2