ArticleMolecular cell2021
ZMYND8-regulated IRF8 transcription axis is an acute myeloid leukemia dependency.
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Article in Molecular cell, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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44 citing papers in PubMed, 63 citations in OpenAlex.
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- CRISPR-based functional genomics for dissecting therapeutic dependency in primary acute myeloid leukemia samples.Molecular cell · 2026Article
- Systematic Evaluation of GAPs and GEFs Identifies a Targetable Dependency for Hematopoietic Malignancies.Cancer discovery · 2025Article
- TRIM63/IRF-8 axis promotes tumor progression and immunosuppression of melanoma with BRAF mutation.Cell death & disease · 2025Article
- Characterization of Chemoresistant Cell Populations Improves Risk Stratification and Therapy Prediction in Pediatric AML.bioRxiv : the preprint server for biology · 2025Article
- ScIsoX: a multidimensional framework for measuring isoform-level transcriptomic complexity in single cells.Genome biology · 2025Article
- ZMYND8 promotes the Warburg effect and tumorigenesis through c-Myc activation in pancreatic cancer.Oncogene · 2025Article
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- Catalytic-independent functions of the Integrator-PP2A complex (INTAC) confer sensitivity to BET inhibition.Nature chemical biology · 2025Article
- Deciphering the role of histone modifications in memory and exhausted CD8 T cells.Scientific reports · 2025Article
- ZMYND8 Reads H3K36me2 to Activate CEBPE Transcription and Suppress Multiple Myeloma Progression through the Inhibition of Adaptive UPR Pathways.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- The RBM39 degrader indisulam inhibits acute megakaryoblastic leukemia by altering the alternative splicing of ZMYND8.Cell & bioscience · 2025Article
- Targeting the histone reader ZMYND8 inhibits antiandrogen-induced neuroendocrine tumor transdifferentiation of prostate cancer.Nature cancer · 2025Article
- Short circuit: Transcription factor addiction as a growing vulnerability in cancer.Current opinion in structural biology · 2024Review
- TET2 germline variants promote kidney disease by impairing DNA repair and activating cytosolic nucleotide sensors.Nature communications · 2024Article
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Authors and funding
22 authors at 5 institutions in 1 country.
Zhendong CaoDepartment of Cancer Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Epigenetics Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Krista A BudinichDepartment of Cancer Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Epigenetics Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Hua HuangEpigenetics Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Diqiu RenDepartment of Cancer Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Epigenetics Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Bin LuCold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
Zhen ZhangEpigenetics Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Qingzhou ChenDepartment of Cancer Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Epigenetics Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Yeqiao ZhouDepartment of Cancer Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Epigenetics Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Yu-Han HuangCold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
Fatemeh AlikaramiDivision of Pediatric Oncology, Department of Pediatrics, Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Molly C KingsleyDivision of Pediatric Oncology, Department of Pediatrics, Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Alexandra K LenardDivision of Pediatric Oncology, Department of Pediatrics, Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Aoi WakabayashiEpigenetics Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Division of Hematology, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Eugene KhandrosEpigenetics Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Division of Hematology, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Will BailisDepartment of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Jun QiDepartment of Cancer Biology, Dana-Farber Cancer Institute, Department of Medicine, Harvard Medical School, Boston, MA 02215, USA.
Martin P CarrollDivision of Hematology and Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Gerd A BlobelEpigenetics Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Division of Hematology, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Robert B FaryabiDepartment of Cancer Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Epigenetics Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Kathrin M BerntDivision of Pediatric Oncology, Department of Pediatrics, Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Shelley L BergerEpigenetics Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Junwei ShiDepartment of Cancer Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Epigenetics Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: jushi@upenn.edu.
University of Pennsylvania · USCancer Research Institute · USChildren's Hospital of Philadelphia · USCold Spring Harbor Laboratory · USHarvard University · US
Funding
Role of PCAF/GCN5 Acetylation on p53 TransactivationR01CA078831 · NCI · WISTAR INSTITUTE · PI BERGER, SHELLEY L · 1999 to 2022
$7.8MHEMATOPOIESIS TRAINING GRANTT32DK007780 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI TONG, WEI · 1999 to 2023
$6.7MStress-modified growth signaling in dynamic nutrient environmentsR35GM138085 · NIGMS · CHILDREN'S HOSP OF PHILADELPHIA · PI Will H. Bailis · 2020 to 2026
$2.7MNCI NIH HHS R01 CA078831NIDDK NIH HHS T32 DK007780NIGMS NIH HHS R35 GM138085
Abstract
The transformed state in acute leukemia requires gene regulatory programs involving transcription factors and chromatin modulators. Here, we uncover an IRF8-MEF2D transcriptional circuit as an acute myeloid leukemia (AML)-biased dependency. We discover and characterize the mechanism by which the chromatin "reader" ZMYND8 directly activates IRF8 in parallel with the MYC proto-oncogene through their lineage-specific enhancers. ZMYND8 is essential for AML proliferation in vitro and in vivo and associates with MYC and IRF8 enhancer elements that we define in cell lines and in patient samples. ZMYND8 occupancy at IRF8 and MYC enhancers requires BRD4, a transcription coactivator also necessary for AML proliferation. We show that ZMYND8 binds to the ET domain of BRD4 via its chromatin reader cassette, which in turn is required for proper chromatin occupancy and maintenance of leukemic growth in vivo. Our results rationalize ZMYND8 as a potential therapeutic target for modulating essential transcriptional programs in AML.
Indexed as
Cell Cycle ProteinsCell LineCell Line, TumorCell ProliferationChromatinEnhancer Elements, GeneticGene Expression Regulation, NeoplasticHumansInterferon Regulatory Factor-8Interferon Regulatory FactorsLeukemia, Myeloid, AcuteNuclear ProteinsPromoter Regions, GeneticProto-Oncogene MasTranscription FactorsTranscription, GeneticCell Cycle ProteinsChromatinInterferon Regulatory Factor-8Interferon Regulatory FactorsMAS1 protein, humanNuclear ProteinsProto-Oncogene MasTranscription FactorsTumor Suppressor ProteinsZMYND8 protein, humanacute myeloid leukemiaepigeneticsIRF8MEF2Dtranscriptional addictionZMYND8
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