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

2.50
Hdl Handle:
http://hdl.handle.net/10033/620678
Title:
A bromodomain-DNA interaction facilitates acetylation-dependent bivalent nucleosome recognition by the BET protein BRDT.
Authors:
Miller, Thomas C R; Simon, Bernd; Rybin, Vladimir; Grötsch, Helga; Curtet, Sandrine; Khochbin, Saadi; Carlomagno, Teresa ( 0000-0002-2437-2760 ) ; Müller, Christoph W
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.
Affiliation:
Helmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany.
Citation:
A bromodomain-DNA interaction facilitates acetylation-dependent bivalent nucleosome recognition by the BET protein BRDT. 2016, 7:13855 Nat Commun
Journal:
Nature communications
Issue Date:
19-Dec-2016
URI:
http://hdl.handle.net/10033/620678
DOI:
10.1038/ncomms13855
PubMed ID:
27991587
Type:
Article
Language:
en
ISSN:
2041-1723
Appears in Collections:
publications of te research group NMR-based structural chemistry (NBSC)

Full metadata record

DC FieldValue Language
dc.contributor.authorMiller, Thomas C Ren
dc.contributor.authorSimon, Bernden
dc.contributor.authorRybin, Vladimiren
dc.contributor.authorGrötsch, Helgaen
dc.contributor.authorCurtet, Sandrineen
dc.contributor.authorKhochbin, Saadien
dc.contributor.authorCarlomagno, Teresaen
dc.contributor.authorMüller, Christoph Wen
dc.date.accessioned2017-01-05T09:27:01Z-
dc.date.available2017-01-05T09:27:01Z-
dc.date.issued2016-12-19-
dc.identifier.citationA bromodomain-DNA interaction facilitates acetylation-dependent bivalent nucleosome recognition by the BET protein BRDT. 2016, 7:13855 Nat Communen
dc.identifier.issn2041-1723-
dc.identifier.pmid27991587-
dc.identifier.doi10.1038/ncomms13855-
dc.identifier.urihttp://hdl.handle.net/10033/620678-
dc.description.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.en
dc.language.isoenen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.titleA bromodomain-DNA interaction facilitates acetylation-dependent bivalent nucleosome recognition by the BET protein BRDT.en
dc.typeArticleen
dc.contributor.departmentHelmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany.en
dc.identifier.journalNature communicationsen

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