A chemical toolbox for the study of bromodomains and epigenetic signaling

Qin Wu, David Heidenreich, Stanley Zhou, Suzanne Ackloo, Andreas Krämer, Kiran Nakka, Evelyne Lima-Fernandes, Genevieve Deblois, Shili Duan, Ravi N. Vellanki, Fengling Li, Masoud Vedadi, Jeffrey Dilworth, Mathieu Lupien, Paul E. Brennan, Cheryl H. Arrowsmith (), Susanne Müller, Oleg Fedorov, Panagis Filippakopoulos and Stefan Knapp ()
Additional contact information
Qin Wu: University of Toronto
David Heidenreich: University of Toronto
Stanley Zhou: University Health Network
Suzanne Ackloo: University of Toronto
Andreas Krämer: Goethe-University Frankfurt
Kiran Nakka: Ottawa Hospital Research Institute
Evelyne Lima-Fernandes: University of Toronto
Genevieve Deblois: University Health Network
Shili Duan: University Health Network
Ravi N. Vellanki: University Health Network
Fengling Li: University of Toronto
Masoud Vedadi: University of Toronto
Jeffrey Dilworth: Ottawa Hospital Research Institute
Mathieu Lupien: University Health Network
Paul E. Brennan: University of Oxford
Cheryl H. Arrowsmith: University of Toronto
Susanne Müller: Goethe-University Frankfurt
Oleg Fedorov: University of Oxford
Panagis Filippakopoulos: University of Oxford
Stefan Knapp: Goethe-University Frankfurt

Nature Communications, 2019, vol. 10, issue 1, 1-14

Abstract: Abstract Bromodomains (BRDs) are conserved protein interaction modules which recognize (read) acetyl-lysine modifications, however their role(s) in regulating cellular states and their potential as targets for the development of targeted treatment strategies is poorly understood. Here we present a set of 25 chemical probes, selective small molecule inhibitors, covering 29 human bromodomain targets. We comprehensively evaluate the selectivity of this probe-set using BROMOscan and demonstrate the utility of the set identifying roles of BRDs in cellular processes and potential translational applications. For instance, we discovered crosstalk between histone acetylation and the glycolytic pathway resulting in a vulnerability of breast cancer cell lines under conditions of glucose deprivation or GLUT1 inhibition to inhibition of BRPF2/3 BRDs. This chemical probe-set will serve as a resource for future applications in the discovery of new physiological roles of bromodomain proteins in normal and disease states, and as a toolset for bromodomain target validation.

Date: 2019
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-019-09672-2 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-09672-2

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-019-09672-2

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().