Journal article
Mapping the chemical chromatin reactivation landscape identifies BRD4-TAF1 cross-talk
- Abstract:
- Bromodomain-containing proteins of the BET family recognize histone lysine acetylation and mediate transcriptional activation of target genes such as the MYC oncogene. Pharmacological inhibitors of BET domains promise therapeutic benefits in a variety of cancers. We performed a high-diversity chemical compound screen for agents capable of modulating BRD4-dependent heterochromatization of a generic reporter in human cells. In addition to known and new compounds targeting BRD4, we identified small molecules that mimic BRD4 inhibition without direct engagement. One such compound was a potent inhibitor of the second bromodomain of TAF1. Using this inhibitor, we discovered that TAF1 synergizes with BRD4 to control proliferation of cancer cells, making TAF1 an attractive epigenetic target in cancers driven by MYC.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Accepted manuscript, pdf, 4.4MB, Terms of use)
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- Publisher copy:
- 10.1038/nchembio.2080
Authors
- Publisher:
- Nature Publishing Group
- Journal:
- Nature Chemical Biology More from this journal
- Volume:
- 12
- Pages:
- 504–510
- Publication date:
- 2016-05-09
- Acceptance date:
- 2016-03-18
- DOI:
- ISSN:
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1552-4450
- Keywords:
- Pubs id:
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pubs:622522
- UUID:
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uuid:0a004f44-4a54-4260-ae0b-98bef7c97cd9
- Local pid:
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pubs:622522
- Source identifiers:
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622522
- Deposit date:
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2016-05-17
- ARK identifier:
Terms of use
- Copyright holder:
- Macmillan Publishers Limited
- Copyright date:
- 2016
- Notes:
-
This is the
accepted manuscript of a journal article published by Nature Publishing Group in Nature Chemical Biology on 2016-03-18, available online: http://dx.doi.org/10.1038/nchembio.2080
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