{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Liu B"],"funding":["Ministry of Science and Technology of the People&apos;&apos;&apos;&apos;s Republic of China","National Natural Science Foundation of China"],"pagination":["e2109133119"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8832982"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["119(6)"],"pubmed_abstract":["BRD4 is well known for its role in super-enhancer organization and transcription activation of several prominent oncogenes including <i>c-MYC</i> and <i>BCL2</i> As such, BRD4 inhibitors are being pursued as promising therapeutics for cancer treatment. However, drug resistance also occurs for BRD4-targeted therapies. Here, we report that BRD4 unexpectedly interacts with the LSD1/NuRD complex and colocalizes with this repressive complex on super-enhancers. Integrative genomic and epigenomic analyses indicate that the BRD4/LSD1/NuRD complex restricts the hyperactivation of a cluster of genes that are functionally linked to drug resistance. Intriguingly, treatment of breast cancer cells with a small-molecule inhibitor of BRD4, JQ1, results in no immediate activation of the drug-resistant gene"],"journal":["Proceedings of the National Academy of Sciences of the United States of America"],"pubmed_title":["BRD4-directed super-enhancer organization of transcription repression programs links to chemotherapeutic efficacy in breast cancer."],"pmcid":["PMC8832982"],"funding_grant_id":["81730079","31991164","1302304"],"pubmed_authors":["Liu X","Wu J","Han L","Zhang Y","Shan L","Yan D","Shang Y","Liu B","Chen X","Liu S","Wang Y","Wu X"],"additional_accession":[]},"is_claimable":false,"name":"BRD4-directed super-enhancer organization of transcription repression programs links to chemotherapeutic efficacy in breast cancer.","description":"BRD4 is well known for its role in super-enhancer organization and transcription activation of several prominent oncogenes including <i>c-MYC</i> and <i>BCL2</i> As such, BRD4 inhibitors are being pursued as promising therapeutics for cancer treatment. However, drug resistance also occurs for BRD4-targeted therapies. Here, we report that BRD4 unexpectedly interacts with the LSD1/NuRD complex and colocalizes with this repressive complex on super-enhancers. Integrative genomic and epigenomic analyses indicate that the BRD4/LSD1/NuRD complex restricts the hyperactivation of a cluster of genes that are functionally linked to drug resistance. Intriguingly, treatment of breast cancer cells with a small-molecule inhibitor of BRD4, JQ1, results in no immediate activation of the drug-resistant gene","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Feb","modification":"2026-06-18T05:59:34.59Z","creation":"2025-04-05T20:07:22.845Z"},"accession":"S-EPMC8832982","cross_references":{"pubmed":["35105803"],"doi":["10.1073/pnas.2109133119"]}}