ArticleNature structural & molecular biology2016
Functional interdependence of BRD4 and DOT1L in MLL leukemia.
Article in Nature structural & molecular biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
70 citing papers in PubMed, 124 citations in OpenAlex.
- Review
- TCA-controlled histone succinylation identifies IDH3B as a prognostic and therapeutic target in AML.Clinical epigenetics · 2026Article
- RBM15B recognizes H3K79me2 to guide selective mThe EMBO journal · 2026Article
- DOT1L provides transcriptional memory through PRC1.1 antagonism.Nature cell biology · 2026Article
- Dot1L licenses DNA demethylation to establish regulatory T cell identity.bioRxiv : the preprint server for biology · 2026Article
- Chromatin Regulatory Targets for Anticancer Therapeutics.Chemical reviews · 2025Review
- Review
- Hiding in plain sight: NUT carcinoma is an unrecognized subtype of squamous cell carcinoma of the lungs and head and neck.Nature reviews. Clinical oncology · 2025Review
- Super-enhancers in tumors: unraveling recent advances in their role in Oncogenesis and the emergence of targeted therapies.Journal of translational medicine · 2025Review
- Recent Developments and Evolving Therapeutic Strategies in KMT2A-Rearranged Acute Leukemia.Cancer medicine · 2024Review
- Application of omics in the diagnosis, prognosis, and treatment of acute myeloid leukemia.Biomarker research · 2024Review
- Distinct Responses to Menin Inhibition and Synergy with DOT1L Inhibition inInternational journal of molecular sciences · 2024Article
- Phase separations in oncogenesis, tumor progressions and metastasis: a glance from hallmarks of cancer.Journal of hematology & oncology · 2023Review
- A guide to epigenetics in leukaemia stem cells.Molecular oncology · 2023Review
- Transcriptional co-activators: emerging roles in signaling pathways and potential therapeutic targets for diseases.Signal transduction and targeted therapy · 2023Review
- CRISPR-ChIP reveals selective regulation of H3K79me2 by Menin in MLL leukemia.Nature structural & molecular biology · 2023Article
- Neointima abating and endothelium preserving - An adventitia-localized nanoformulation to inhibit the epigenetic writer DOT1L.Biomaterials · 2023Article
- Defining super-enhancers by highly ranked histone H4 multi-acetylation levels identifies transcription factors associated with glioblastoma stem-like properties.BMC genomics · 2023Article
- ACC010, a novel BRD4 inhibitor, synergized with homoharringtonine in acute myeloid leukemia with FLT3-ITD.Molecular oncology · 2023Article
- DOT1L regulates chromatin reorganization and gene expression during sperm differentiation.EMBO reports · 2023Article
10 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
31 authors at 8 institutions in 5 countries.
Funding
Abstract
Targeted therapies against disruptor of telomeric silencing 1-like (DOT1L) and bromodomain-containing protein 4 (BRD4) are currently being evaluated in clinical trials. However, the mechanisms by which BRD4 and DOT1L regulate leukemogenic transcription programs remain unclear. Using quantitative proteomics, chemoproteomics and biochemical fractionation, we found that native BRD4 and DOT1L exist in separate protein complexes. Genetic disruption or small-molecule inhibition of BRD4 and DOT1L showed marked synergistic activity against MLL leukemia cell lines, primary human leukemia cells and mouse leukemia models. Mechanistically, we found a previously unrecognized functional collaboration between DOT1L and BRD4 that is especially important at highly transcribed genes in proximity to superenhancers. DOT1L, via dimethylated histone H3 K79, facilitates histone H4 acetylation, which in turn regulates the binding of BRD4 to chromatin. These data provide new insights into the regulation of transcription and specify a molecular framework for therapeutic intervention in this disease with poor prognosis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.