{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Shah V"],"funding":["European Research Council","Medical Research Council","Wellcome Trust"],"pagination":["748-764"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC7618521"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["145(7)"],"pubmed_abstract":["<h4>Abstract</h4>Initial clinical trials with drugs targeting epigenetic modulators, such as bromodomain and extraterminal protein (BET) inhibitors, demonstrate modest results in acute myeloid leukemia (AML). A major reason for this involves an increased transcriptional plasticity within AML, which allows the cells to escape therapeutic pressure. In this study, we investigated the immediate epigenetic and transcriptional responses after BET inhibition and demonstrated that BET inhibitor-mediated release of bromodomain-containing protein 4 from chromatin is accompanied by acute compensatory feedback that attenuates downregulation or even increases the expression of specific transcriptional modules. This adaptation is marked at key AML maintenance genes and is mediated by p300, suggesting a "],"journal":["Blood"],"pubmed_title":["Acute resistance to BET inhibitors remodels compensatory transcriptional programs via p300 coactivation."],"pmcid":["PMC7618521"],"funding_grant_id":["203151/Z/16/Z","205254","647685","MR/R009708/1","205254/Z/16/Z"],"pubmed_authors":["Haehnel PS","Kindler T","Yun H","Dhar A","Horton SJ","Behrendt MA","Agrawal-Singh S","Dawson MA","Meyerhofer M","Kuhn MWM","Gallego-Crespo A","Shah V","Schubert B","Basheer F","Guezguez B","Gallipoli P","Prinjha RK","Tarkar A","Lugo D","Eleftheriadou I","Sasca D","Huntly BJP","Osaki H","Barbash O","Saura-Panella M","Theobald M","Yeh P","Giotopoulos G","Meduri E"],"additional_accession":[]},"is_claimable":false,"name":"Acute resistance to BET inhibitors remodels compensatory transcriptional programs via p300 coactivation.","description":"<h4>Abstract</h4>Initial clinical trials with drugs targeting epigenetic modulators, such as bromodomain and extraterminal protein (BET) inhibitors, demonstrate modest results in acute myeloid leukemia (AML). A major reason for this involves an increased transcriptional plasticity within AML, which allows the cells to escape therapeutic pressure. In this study, we investigated the immediate epigenetic and transcriptional responses after BET inhibition and demonstrated that BET inhibitor-mediated release of bromodomain-containing protein 4 from chromatin is accompanied by acute compensatory feedback that attenuates downregulation or even increases the expression of specific transcriptional modules. This adaptation is marked at key AML maintenance genes and is mediated by p300, suggesting a ","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Feb","modification":"2026-06-08T05:04:36.978Z","creation":"2026-06-08T03:08:52.096Z"},"accession":"S-EPMC7618521","cross_references":{"pubmed":["39651888"],"doi":["10.1182/blood.2022019306"]}}