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- W1526798002 abstract "The bromodomain and extraterminal (BET) protein BRD4 is a validated drug target in leukemia, yet its regulatory function in this disease is not well understood. Here, we show that BRD4 chromatin occupancy in acute myeloid leukemia closely correlates with the hematopoietic transcription factors (TFs) PU.1, FLI1, ERG, C/EBPα, C/EBPβ, and MYB at nucleosome-depleted enhancer and promoter regions. We provide evidence that these TFs, in conjunction with the lysine acetyltransferase activity of p300/CBP, facilitate BRD4 recruitment to their occupied sites to promote transcriptional activation. Chemical inhibition of BET bromodomains was found to suppress the functional output of each hematopoietic TF, thereby interfering with essential lineage-specific transcriptional circuits in this disease. These findings reveal a chromatin-based signaling cascade comprised of hematopoietic TFs, p300/CBP, and BRD4 that supports leukemia maintenance and is suppressed by BET bromodomain inhibition." @default.
- W1526798002 created "2016-06-24" @default.
- W1526798002 creator A5015010943 @default.
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- W1526798002 date "2015-06-01" @default.
- W1526798002 modified "2023-10-14" @default.
- W1526798002 title "BET Bromodomain Inhibition Suppresses the Function of Hematopoietic Transcription Factors in Acute Myeloid Leukemia" @default.
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- W1526798002 doi "https://doi.org/10.1016/j.molcel.2015.04.011" @default.
- W1526798002 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4475489" @default.
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