BRD4 bimodal binding at promoters and drug-induced displacement at Pol II pause sites associates with I-BET sensitivity.

P KhoueiryA Ward GahlawatM PetretichA M MichonD SimolaE LamE E FurlongV BenesM A DawsonR K PrinjhaG DrewesPaola Grandi

Published in: Epigenetics & chromatin (2019)

We provide evidence that I-BET-induced shift of Pol II pausing at promoters via displacement of BRD4 is a determinant of intrinsic I-BET sensitivity. This finding may guide pharmacological treatment to enhance the clinical utility of such targeted therapies in AML and potentially other BET proteins-driven diseases.

Keyphrases

drug induced
liver injury
acute myeloid leukemia
diabetic rats
high glucose
adverse drug
oxidative stress
transcription factor
binding protein
acute lymphoblastic leukemia
combination therapy
dna binding