Mapping the chemical chromatin reactivation landscape identifies BRD4-TAF1 cross-talk.
Nat Chem Biol
; 12(7): 504-10, 2016 07.
Article
en En
| MEDLINE
| ID: mdl-27159579
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.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Factores de Transcripción
/
Proteínas Nucleares
/
Cromatina
/
Factores Asociados con la Proteína de Unión a TATA
/
Factor de Transcripción TFIID
/
Histona Acetiltransferasas
/
Bibliotecas de Moléculas Pequeñas
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Nat Chem Biol
Asunto de la revista:
BIOLOGIA
/
QUIMICA
Año:
2016
Tipo del documento:
Article
País de afiliación:
Austria