A bromodomain-DNA interaction facilitates acetylation-dependent bivalent nucleosome recognition by the BET protein BRDT.
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
AuthorsMiller, Thomas C R
Müller, Christoph W
MetadataShow full item record
AbstractBromodomains 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.
CitationA bromodomain-DNA interaction facilitates acetylation-dependent bivalent nucleosome recognition by the BET protein BRDT. 2016, 7:13855 Nat Commun
AffiliationHelmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany.
The following license files are associated with this item:
- Creative Commons
Except where otherwise noted, this item's license is described as http://creativecommons.org/licenses/by-nc-sa/4.0/
- Solution structure of the second bromodomain of Brd2 and its specific interaction with acetylated histone tails.
- Authors: Huang H, Zhang J, Shen W, Wang X, Wu J, Wu J, Shi Y
- Issue date: 2007 Sep 12
- Cooperative binding of two acetylation marks on a histone tail by a single bromodomain.
- Authors: Morinière J, Rousseaux S, Steuerwald U, Soler-López M, Curtet S, Vitte AL, Govin J, Gaucher J, Sadoul K, Hart DJ, Krijgsveld J, Khochbin S, Müller CW, Petosa C
- Issue date: 2009 Oct 1
- Metabolically Derived Lysine Acylations and Neighboring Modifications Tune the Binding of the BET Bromodomains to Histone H4.
- Authors: Olp MD, Zhu N, Smith BC
- Issue date: 2017 Oct 17
- Affinity map of bromodomain protein 4 (BRD4) interactions with the histone H4 tail and the small molecule inhibitor JQ1.
- Authors: Jung M, Philpott M, Müller S, Schulze J, Badock V, Eberspächer U, Moosmayer D, Bader B, Schmees N, Fernández-Montalván A, Haendler B
- Issue date: 2014 Mar 28
- Structural basis and binding properties of the second bromodomain of Brd4 with acetylated histone tails.
- Authors: Liu Y, Wang X, Zhang J, Huang H, Ding B, Wu J, Shi Y
- Issue date: 2008 Jun 17