ArticleMolecular cell2021
Targeting histone acetylation dynamics and oncogenic transcription by catalytic P300/CBP inhibition.
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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 107 papers, 1 of them a synthesis that pooled it.
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107citing papers in PubMed, 1 pooled it
9.9field-weighted citation impact, top 1% of its field
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Who cites it
107 citing papers in PubMed, 1 synthesis or guideline pooled it, 160 citations in OpenAlex.
- P300 Event-Related Potentials as Cognitive Biomarkers in Neurological and Neuropsychiatric Disorders: A Systematic Review.Revista de neurologia · 2026Pooled it
- Review
- Chromatin modifiers KMT2D, cBAF, and p300 cooperatively facilitate de novo binding of transcription factors on enhancers.Nature communications · 2026Article
- EZH2 inhibition overcomes immunomodulatory drug resistance in multiple myeloma via a cereblon-dependent pathway.Haematologica · 2026Article
- H2AC19 promotes lung adenocarcinoma progressionActa pharmaceutica Sinica. B · 2026Article
- Understanding the epigenetic regulation of lactylation and aberrant lactate metabolism in cancer: From mechanisms to therapeutic strategies (Review).International journal of oncology · 2026Review
- Transcription factor targeting strategies in cancer: mechanisms, challenges and cutting-edge progress.Acta pharmacologica Sinica · 2026Review
- Epigenetic mechanisms of inflammatory memory in the central nervous system.Nature immunology · 2026Review
- An orally active dual CBP/p300 degrader targets core dependencies of multiple myeloma.Cell reports · 2026Article
- Lysine lactylation-mediated post-translational modification: Molecular mechanisms and therapeutic target exploration in tumour drug resistance.Clinical and translational medicine · 2026Review
- Endometrial NCOR1 deficiency contributes to implantation failure in endometriosis-associated infertility.iScience · 2026Article
- CpG island density predicts CBP/p300 dependency across 3D chromatin clusters.bioRxiv : the preprint server for biology · 2026Article
- BCR::ABL1-Induced Enhancer Reprogramming Uncovers Hypersensitivity of Ph+B-ALL Cells to Enhancer-Targeting Drugs.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- KDM6A promotes diabetic retinopathy via H3K27me3-dependent ferroptosis in Müller cells.Cell death & disease · 2026Article
- Genetic and Epigenetic Mechanisms Underlying Reversible Adaptive Responses in Fungi.Journal of fungi (Basel, Switzerland) · 2026Review
- The impact of fulvestrant on estrogen receptor-driven chromatin dynamics in breast cancer cells.Epigenetics & chromatin · 2026Article
- A Modular Platform for Effector Discovery in Induced-Proximity Lysine Acetylation.bioRxiv : the preprint server for biology · 2026Article
- HDAC3 Preserves the primordial follicle reserve by epigenetically suppressing ferroptosis in pregranulosa cells.Cellular and molecular life sciences : CMLS · 2026Article
- Article
- Catalytic Inhibition of p300 Preferentially Targets IRF4 Oncogenic Activity and Tumor Growth in Multiple Myeloma.Cancer research · 2026Article
47 more citing papers are in PubMed but not listed here.
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Authors and funding
42 authors at 11 institutions in 2 countries.
Simon J HoggTranslational Hematology Program, Gene Regulation Laboratory, Peter MacCallum Cancer Center, Melbourne, 3000, Australia; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, 3000, Australia; Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Olga MotornaTranslational Hematology Program, Gene Regulation Laboratory, Peter MacCallum Cancer Center, Melbourne, 3000, Australia; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, 3000, Australia; Monash Haematology, Monash Health, Clayton, 3168, Australia; School of Clinical Sciences at Monash Health, Monash University, Clayton, 3800, Australia.
Leonie A CluseTranslational Hematology Program, Gene Regulation Laboratory, Peter MacCallum Cancer Center, Melbourne, 3000, Australia.
Timothy M JohansonThe Walter and Eliza Hall Institute of Medical Research, Parkville, 3052, Australia; Department of Medical Biology, The University of Melbourne, Parkville, 3010, Australia.
Hannah D CoughlanThe Walter and Eliza Hall Institute of Medical Research, Parkville, 3052, Australia; Department of Medical Biology, The University of Melbourne, Parkville, 3010, Australia.
Ramya RaviramNew York Genome Center, New York, NY 10013, USA.
Robert M MyersTri-Institutional MD-PhD Program, Weill Cornell Medicine, Rockefeller University, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA.
Matteo CostacurtaTranslational Hematology Program, Gene Regulation Laboratory, Peter MacCallum Cancer Center, Melbourne, 3000, Australia; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, 3000, Australia.
Izabela TodorovskiTranslational Hematology Program, Gene Regulation Laboratory, Peter MacCallum Cancer Center, Melbourne, 3000, Australia; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, 3000, Australia.
Lizzy PijpersTranslational Hematology Program, Gene Regulation Laboratory, Peter MacCallum Cancer Center, Melbourne, 3000, Australia; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, 3000, Australia.
Stefan BjelosevicTranslational Hematology Program, Gene Regulation Laboratory, Peter MacCallum Cancer Center, Melbourne, 3000, Australia; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, 3000, Australia.
Tobias WilliamsSir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, 3000, Australia; RNA Biology and Cancer Laboratory, Peter MacCallum Cancer Centre, Melbourne, 3000, Australia.
Shannon N HuskinsTasmanian School of Medicine, College of Health and Medicine, University of Tasmania, Hobart, 7000, Australia.
Conor J KearneyTranslational Hematology Program, Gene Regulation Laboratory, Peter MacCallum Cancer Center, Melbourne, 3000, Australia; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, 3000, Australia.
Jennifer R DevlinTranslational Hematology Program, Gene Regulation Laboratory, Peter MacCallum Cancer Center, Melbourne, 3000, Australia; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, 3000, Australia.
Zheng FanTranslational Hematology Program, Gene Regulation Laboratory, Peter MacCallum Cancer Center, Melbourne, 3000, Australia; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, 3000, Australia.
Jafar S JabbariDepartment of Microbiology and Immunology, The University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne, 3000, Australia.
Ben P MartinTranslational Hematology Program, Gene Regulation Laboratory, Peter MacCallum Cancer Center, Melbourne, 3000, Australia.
Mohamed FarehTranslational Hematology Program, Gene Regulation Laboratory, Peter MacCallum Cancer Center, Melbourne, 3000, Australia; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, 3000, Australia.
Madison J KellyTranslational Hematology Program, Gene Regulation Laboratory, Peter MacCallum Cancer Center, Melbourne, 3000, Australia; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, 3000, Australia.
Daphné Dupéré-RicherDivision of Hematology/Oncology, The University of Florida Health Cancer Center, Gainesville, FL 32608, USA.
Jarrod J SandowThe Walter and Eliza Hall Institute of Medical Research, Parkville, 3052, Australia; Department of Medical Biology, The University of Melbourne, Parkville, 3010, Australia.
Breon FeranThe Walter and Eliza Hall Institute of Medical Research, Parkville, 3052, Australia; Department of Medical Biology, The University of Melbourne, Parkville, 3010, Australia.
Deborah KnightTranslational Hematology Program, Gene Regulation Laboratory, Peter MacCallum Cancer Center, Melbourne, 3000, Australia.
Tiffany KhongAustralian Center for Blood Diseases, Monash University, Melbourne, 3004, Australia.
Andrew SpencerAustralian Center for Blood Diseases, Monash University, Melbourne, 3004, Australia.
Simon J HarrisonSir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, 3000, Australia; Clinical Hematology, Peter MacCallum Cancer Center, Melbourne, 3000, Australia; Royal Melbourne Hospital, Melbourne, 3000, Australia.
Gareth GregoryMonash Haematology, Monash Health, Clayton, 3168, Australia; School of Clinical Sciences at Monash Health, Monash University, Clayton, 3800, Australia.
Vihandha O WickramasingheSir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, 3000, Australia; RNA Biology and Cancer Laboratory, Peter MacCallum Cancer Centre, Melbourne, 3000, Australia.
Andrew I WebbThe Walter and Eliza Hall Institute of Medical Research, Parkville, 3052, Australia; Department of Medical Biology, The University of Melbourne, Parkville, 3010, Australia.
Phillippa C TaberlayTasmanian School of Medicine, College of Health and Medicine, University of Tasmania, Hobart, 7000, Australia.
Kenneth D BrombergDiscovery, Global Pharmaceutical Research and Development, AbbVie, North Chicago, IL 60064, USA.
Albert LaiDiscovery, Global Pharmaceutical Research and Development, AbbVie, North Chicago, IL 60064, USA.
Anthony T PapenfussSir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, 3000, Australia; The Walter and Eliza Hall Institute of Medical Research, Parkville, 3052, Australia; Department of Medical Biology, The University of Melbourne, Parkville, 3010, Australia.
Gordon K SmythThe Walter and Eliza Hall Institute of Medical Research, Parkville, 3052, Australia; School of Mathematics and Statistics, The University of Melbourne, Parkville, 3010, Australia.
Rhys S AllanThe Walter and Eliza Hall Institute of Medical Research, Parkville, 3052, Australia; Department of Medical Biology, The University of Melbourne, Parkville, 3010, Australia.
Jonathan D LichtDivision of Hematology/Oncology, The University of Florida Health Cancer Center, Gainesville, FL 32608, USA.
Dan A LandauNew York Genome Center, New York, NY 10013, USA; Division of Hematology and Medical Oncology, Department of Medicine, Weill Cornell Medicine, New York, NY 10021, USA.
Omar Abdel-WahabHuman Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Jake ShorttSir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, 3000, Australia; Monash Haematology, Monash Health, Clayton, 3168, Australia; School of Clinical Sciences at Monash Health, Monash University, Clayton, 3800, Australia.
Stephin J VervoortTranslational Hematology Program, Gene Regulation Laboratory, Peter MacCallum Cancer Center, Melbourne, 3000, Australia; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, 3000, Australia. Electronic address: stephin.vervoort@petermac.org.
Ricky W JohnstoneTranslational Hematology Program, Gene Regulation Laboratory, Peter MacCallum Cancer Center, Melbourne, 3000, Australia; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, 3000, Australia. Electronic address: ricky.johnstone@petermac.org.
The University of Melbourne · AUMemorial Sloan Kettering Cancer Center · USPeter MacCallum Cancer Centre · AUAbbVie (United States) · USAustralian Centre for HIV and Hepatitis Virology Research · AUUniversity of Florida Health · USUniversity of Tasmania · AUCornell University · USMonash Health · AUNew York Genome Center · USThe Royal Melbourne Hospital · AU
Funding
X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Hongbiao Carl Lekaye · 1985 to 2026
$347.4MWeill Cornell/Rockefeller/Sloan-Kettering MST ProgramT32GM007739 · NIGMS · WEILL MEDICAL COLL OF CORNELL UNIV · PI HSU, KATHARINE C · 1985 to 2023
$51.1MUTX, MLL AND PATHOGENIC DEREGULATION OF HISTONE METHYLATION IN MULTIPLE MYELOMAR01CA180475 · NCI · UNIVERSITY OF FLORIDA · PI LICHT, JONATHAN D. · 2014 to 2020
$1.8MNCI NIH HHS P30 CA008748NCI NIH HHS R01 CA180475NIGMS NIH HHS T32 GM007739
Abstract
To separate causal effects of histone acetylation on chromatin accessibility and transcriptional output, we used integrated epigenomic and transcriptomic analyses following acute inhibition of major cellular lysine acetyltransferases P300 and CBP in hematological malignancies. We found that catalytic P300/CBP inhibition dynamically perturbs steady-state acetylation kinetics and suppresses oncogenic transcriptional networks in the absence of changes to chromatin accessibility. CRISPR-Cas9 screening identified NCOR1 and HDAC3 transcriptional co-repressors as the principal antagonists of P300/CBP by counteracting acetylation turnover kinetics. Finally, deacetylation of H3K27 provides nucleation sites for reciprocal methylation switching, a feature that can be exploited therapeutically by concomitant KDM6A and P300/CBP inhibition. Overall, this study indicates that the steady-state histone acetylation-methylation equilibrium functions as a molecular rheostat governing cellular transcription that is amenable to therapeutic exploitation as an anti-cancer regimen.
Indexed as
BiocatalysisOncogenesTranscription, GeneticAcetylationCell LineChromatinConserved SequenceCo-Repressor ProteinsEvolution, MolecularGene Regulatory NetworksGenomeHistone Deacetylase 3Histone DeacetylasesHistonesHumansKineticsChromatinCo-Repressor ProteinsHistone Deacetylase 3Histone DeacetylasesHistonesp300-CBP Transcription FactorsRNA Polymerase IIcancerchromatin biologyepigeneticsH3K27achistone acetylationhistone deacetylasehistone methylationlysine acetylationP300/CBPtranscription
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