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  • Review Article
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Bromodomain biology and drug discovery

Nature Structural & Molecular Biology volume 26, pages 870–879 (2019)Cite this article

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Abstract

The bromodomain (BrD) is a conserved structural module found in chromatin- and transcription-associated proteins that acts as the primary reader for acetylated lysine residues. This basic activity endows BrD proteins with versatile functions in the regulation of protein-protein interactions mediating chromatin-templated gene transcription, DNA recombination, replication and repair. Consequently, BrD proteins are involved in the pathogenesis of numerous human diseases. In this Review, we highlight our current understanding of BrD biology, and discuss the latest development of small-molecule inhibitors targeting BrDs as emerging epigenetic therapies for cancer and inflammatory disorders.

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Fig. 1: Three-dimensional structure and Kac binding mode of the bromodomain.
Fig. 2: Classification of BrD-containing proteins based on major known functions.
Fig. 3: 3D structures of representative BrDs in different forms.
Fig. 4: Representative small-molecule inhibitors and PROTACs for selected BrDs.
Fig. 5: Illustrative diagram highlighting representative functions of nine subclasses of human BrD proteins.

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Acknowledgements

We thank members of the Zhou group for helpful discussion and C. Kim for preparing Supplementary Tables 1 and 2. This work was supported in part by the research grants from the National Institutes of Health (to M.-M.Z. and N.Z.).

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  1. Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Nilesh Zaware & Ming-Ming Zhou

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  1. Nilesh Zaware
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Correspondence to Ming-Ming Zhou.

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M.-M.Z. is a founder, director and shareholder of Parkside Scientific Inc.

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Zaware, N., Zhou, MM. Bromodomain biology and drug discovery. Nat Struct Mol Biol 26, 870–879 (2019). https://doi.org/10.1038/s41594-019-0309-8

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