PerspectiveBromodomain Histone Readers and Cancer

- Lysine acetylation of histone proteins is a fundamental post-translational modification that regulates chromatin structure and plays an important role in gene transcription.
- Histone lysine acetylation at specific loci is associated with cancers.
- Acetyl-lysine modifications create docking sites for bromodomains, which are structurally conserved modules present in “reader” proteins.
- Bromodomain-containing reader proteins have emerged as attractive targets for cancer drug discovery.
- Here, we describe bromodomain-containing proteins with defined roles in cancer and highlight recent progress in the development of bromodomain inhibitors.

Lysine acetylation of histone proteins is a fundamental post-translational modification that regulates chromatin structure and plays an important role in gene transcription. Aberrant levels of histone lysine acetylation are associated with the development of several diseases. Acetyl-lysine modifications create docking sites for bromodomains, which are structurally conserved modules present in transcription-associated proteins that are termed “reader” proteins. Bromodomain-containing reader proteins are part of multiprotein complexes that regulate transcription programs, which are often associated with profound phenotypic changes. Many bromodomain-containing proteins are aberrantly expressed in diseases, as best studied in cancers, where bromodomain proteins impact the expression of oncogenes and anti-apoptotic proteins. Thus, bromodomain readers of histone acetylation have emerged as attractive targets for cancer drug discovery, prompting immense interest in epigenetic-focused, medicinal chemistry to develop structurally guided chemical probes of bromodomains. Here, we describe bromodomain-containing proteins with defined roles in cancer and highlight recent progress in the development of bromodomain inhibitors.

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