A bromodomain–DNA interaction facilitates acetylation-dependent bivalent nucleosome recognition by the BET protein BRDT

Bromodomains are critical components of many chromatin modifying/remodelling proteins and are emerging therapeutic targets, yet how they interact with nucleosomes, rather than acetylated peptides, remains unclear. Using BRDT as a model, we characterized how the BET family of bromodomains interacts with site-specifically acetylated nucleosomes. Here we report that BRDT interacts with nucleosomes through its first (BD1), but not second (BD2) bromodomain, and that acetylated histone recognition by BD1 is complemented by a bromodomain–DNA interaction. Simultaneous DNA and histone recognition enhances BRDT’s nucleosome binding affinity and specificity, and its ability to localize to acetylated chromatin in cells. Conservation of DNA binding in bromodomains of BRD2, BRD3 and BRD4, indicates that bivalent nucleosome recognition is a key feature of these bromodomains and possibly others. Our results elucidate the molecular mechanism of BRDT association with nucleosomes and identify structural features of the BET bromodomains that may be targeted for therapeutic inhibition. Many chromatin modifying proteins, including BRDT, contain bromodomains, which are known to interact with nucleosomes. Here, the authors find that BRDT interacts with nucleosomes via only one of its two bromodomains, and that the interaction involves contacts with DNA as well as acetylated histones.

• Publication year

  2016

• Venue

  Nature Communications

• Publication date

  2016-09-12

• Fields of study

  Biology, Medicine, Chemistry

• Identifiers
  DOI 10.1038/ncomms13855PMID 27991587PMCID 5187433
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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