Mapping the chemical chromatin reactivation landscape identifies BRD4-TAF1 cross-talk
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 chemic...
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| Format: | Journal article |
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Nature Publishing Group
2016
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| _version_ | 1797052475423850496 |
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| author | Huber, K Knapp, S Fedorov, O |
| author_facet | Huber, K Knapp, S Fedorov, O |
| author_sort | Huber, K |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-06T18:32:06Z |
| format | Journal article |
| id | oxford-uuid:0a004f44-4a54-4260-ae0b-98bef7c97cd9 |
| institution | University of Oxford |
| last_indexed | 2024-03-06T18:32:06Z |
| publishDate | 2016 |
| publisher | Nature Publishing Group |
| record_format | dspace |
| spelling | oxford-uuid:0a004f44-4a54-4260-ae0b-98bef7c97cd92022-03-26T09:21:26ZMapping the chemical chromatin reactivation landscape identifies BRD4-TAF1 cross-talkJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:0a004f44-4a54-4260-ae0b-98bef7c97cd9Symplectic Elements at OxfordNature Publishing Group2016Huber, KKnapp, SFedorov, OBromodomain-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. |
| spellingShingle | Huber, K Knapp, S Fedorov, O Mapping the chemical chromatin reactivation landscape identifies BRD4-TAF1 cross-talk |
| title | Mapping the chemical chromatin reactivation landscape identifies BRD4-TAF1 cross-talk |
| title_full | Mapping the chemical chromatin reactivation landscape identifies BRD4-TAF1 cross-talk |
| title_fullStr | Mapping the chemical chromatin reactivation landscape identifies BRD4-TAF1 cross-talk |
| title_full_unstemmed | Mapping the chemical chromatin reactivation landscape identifies BRD4-TAF1 cross-talk |
| title_short | Mapping the chemical chromatin reactivation landscape identifies BRD4-TAF1 cross-talk |
| title_sort | mapping the chemical chromatin reactivation landscape identifies brd4 taf1 cross talk |
| work_keys_str_mv | AT huberk mappingthechemicalchromatinreactivationlandscapeidentifiesbrd4taf1crosstalk AT knapps mappingthechemicalchromatinreactivationlandscapeidentifiesbrd4taf1crosstalk AT fedorovo mappingthechemicalchromatinreactivationlandscapeidentifiesbrd4taf1crosstalk |