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

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Miller, T.C.R.; Simon, B.; Rybin, V.; Grötsch, H.; Curtet, S. et al.: A bromodomain-DNA interaction facilitates acetylation-dependent bivalent nucleosome recognition by the BET protein BRDT. In: Nature Communications 7 (2016), 13855. DOI: https://doi.org/10.1038/ncomms13855

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Abstract: 
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.
License of this version: CC BY 4.0
Document Type: article
Publishing status: publishedVersion
Issue Date: 2016
Appears in Collections:Naturwissenschaftliche Fakultät

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pos. country downloads
total perc.
1 image of flag of Germany Germany 603 94.51%
2 image of flag of Indonesia Indonesia 5 0.78%
3 image of flag of No geo information available No geo information available 4 0.63%
4 image of flag of Russian Federation Russian Federation 4 0.63%
5 image of flag of Europe Europe 4 0.63%
6 image of flag of United States United States 2 0.31%
7 image of flag of United Kingdom United Kingdom 2 0.31%
8 image of flag of China China 2 0.31%
9 image of flag of Canada Canada 2 0.31%
10 image of flag of Thailand Thailand 1 0.16%
    other countries 9 1.41%

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