ArticleMolecular cell2018
MLL4 Is Required to Maintain Broad H3K4me3 Peaks and Super-Enhancers at Tumor Suppressor Genes.
Open access · bronzeAbstract read
In one paragraph
Article in Molecular cell, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 105 papers.
0numbers the graph read from it
0cells of the map it votes in
105citing papers in PubMed
6.9field-weighted citation impact, top 2% of its field
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
105 citing papers in PubMed, 154 citations in OpenAlex.
- UDP-glucuronate decarboxylase 1 promotes tumor immune evasion by accelerating KMT2D loss in hepatocellular carcinoma.Journal for immunotherapy of cancer · 2026Article
- The H3K4 methyltransferase KMT2D is an essential cofactor for GATA1 at erythroid gene enhancers.Nature communications · 2026Article
- Developmental determinants of male bias in medulloblastoma.bioRxiv : the preprint server for biology · 2026Article
- CFP1-mediated H3K4me3 broad domains control early B cell lineage fate determination.Nucleic acids research · 2026Article
- Article
- KMT2D temporally activates neuronal transcriptional factor genes to mediate cerebellar granule cell differentiation.Science advances · 2025Article
- HIF-independent oxygen sensing via KDM6A regulates ferroptosis.Molecular cell · 2025Article
- Identification of TMEM100's role in immune infiltration regulation and construction of an endogenous RNA network in prostate cancer through pan-cancer analysis.Discover oncology · 2025Article
- Heterozygous Kmt2d loss diminishes enhancers to render medulloblastoma cells vulnerable to combinatory inhibition of LSD1 and OXPHOS.Cell reports · 2025Article
- Genetic abnormalities predict outcomes in patients with core binding factor acute myeloid leukemia.Annals of hematology · 2025Article
- Epigenetic modifications and their roles in pediatric brain tumor formation: emerging insights from chromatin dysregulation.Frontiers in oncology · 2025Review
- Super-enhancer DNA methylation in cancer: the mechanism of action and therapeutic directions.Frontiers in oncology · 2025Review
- Mll4 in skeletal muscle fibers maintains muscle stem cells.Skeletal muscle · 2024Article
- Epigenetic Modifiers: Exploring the Roles of Histone Methyltransferases and Demethylases in Cancer and Neurodegeneration.Biology · 2024Review
- Mapping in silico genetic networks of the KMT2D tumour suppressor gene to uncover novel functional associations and cancer cell vulnerabilities.Genome medicine · 2024Article
- Dietary Organic Zinc Supplementation Modifies the Oxidative Genes via RORγ and Epigenetic Regulations in the Ileum of Broiler Chickens Exposed to High-Temperature Stress.Antioxidants (Basel, Switzerland) · 2024Article
- Phase separation of PML/RARα and BRD4 coassembled microspeckles governs transcriptional dysregulation in acute promyelocytic leukemia.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Histone-methyltransferase KMT2D deficiency impairs the Fanconi anemia/BRCA pathway upon glycolytic inhibition in squamous cell carcinoma.Nature communications · 2024Article
- The COMPASS complex maintains the metastatic capacity imparted by a subpopulation of cells in UPS.iScience · 2024Article
- On the Boundary of Exploratory Genomics and Translation in Sequential Glioblastoma.International journal of molecular sciences · 2024Article
45 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
18 authors at 10 institutions in 1 country.
Shilpa S DharDepartment of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
Dongyu ZhaoInstitute for Academic Medicine, The Methodist Hospital Research Institute, Houston, TX 77030, USA; Center for Cardiovascular Regeneration, Department of Cardiovascular Sciences, The Methodist Hospital Research Institute, Houston, TX 77030, USA; Weill Cornell Medical College, Cornell University, New York, NY 10065, USA.
Tao LinDepartment of Pathology and Immunology, Department of Neuroscience, Program in Developmental Biology, Baylor College of Medicine, Jan and Dan Duncan Neurological Research Institute of Texas Children's Hospital, Houston, TX 77030, USA.
Bingnan GuDepartment of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
Khusboo PalDepartment of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
Sarah J WuDepartment of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA; The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, TX 77030, USA.
Hunain AlamDepartment of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
Jie LvInstitute for Academic Medicine, The Methodist Hospital Research Institute, Houston, TX 77030, USA; Center for Cardiovascular Regeneration, Department of Cardiovascular Sciences, The Methodist Hospital Research Institute, Houston, TX 77030, USA; Weill Cornell Medical College, Cornell University, New York, NY 10065, USA.
Kyuson YunInstitute for Academic Medicine, The Methodist Hospital Research Institute, Houston, TX 77030, USA; Weill Cornell Medical College, Cornell University, New York, NY 10065, USA; Department of Neurosurgery, The Methodist Hospital Research Institute, Houston, TX 77030, USA.
Vidya GopalakrishnanDepartment of Pediatrics - Research, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
Elsa R FloresDepartment of Molecular Oncology and Cancer Biology and Evolution Program, Moffitt Cancer Center, 12902 Magnolia Drive, Tampa, FL 33612, USA.
Paul A NorthcottDevelopmental Neurobiology, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105, USA.
Veena RajaramDepartment of Pathology, The University of Texas Southwestern Medical Center, Dallas, TX 75235, USA.
Wei LiDivision of Biostatistics, Dan L. Duncan Cancer Center and Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
Ali ShilatifardDepartment of Biochemistry and Molecular Genetics, Northwestern University, Chicago, IL 60611, USA.
Roy V SillitoeDepartment of Pathology and Immunology, Department of Neuroscience, Program in Developmental Biology, Baylor College of Medicine, Jan and Dan Duncan Neurological Research Institute of Texas Children's Hospital, Houston, TX 77030, USA.
Kaifu ChenInstitute for Academic Medicine, The Methodist Hospital Research Institute, Houston, TX 77030, USA; Center for Cardiovascular Regeneration, Department of Cardiovascular Sciences, The Methodist Hospital Research Institute, Houston, TX 77030, USA; Weill Cornell Medical College, Cornell University, New York, NY 10065, USA. Electronic address: kchen2@houstonmethodist.org.
Min Gyu LeeDepartment of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA; The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, TX 77030, USA. Electronic address: mglee@mdanderson.org.
The University of Texas MD Anderson Cancer Center · USCornell University · USBaylor College of Medicine · USHouston Methodist · USMoffitt Cancer Center · USNorthwestern University · USSt. Jude Children's Research Hospital · USTexas Children's Hospital · USThe University of Texas Southwestern Medical Center · USUniversity of Houston · US
Funding
Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Fabien Delerue · 1985 to 2026
$290.8MMutations of Chromatin and its Modifying Machineries in MalignanciesR35CA197569 · NCI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI Ali Shilatifard · 2015 to 2026
$10.7MSteps towards a paternal gene activation therapy for Angelman syndromeU54HD083092 · NICHD · BAYLOR COLLEGE OF MEDICINE · PI ARENKIEL, BENJAMIN R, NELSON, DAVID LOREN · 2014 to 2019
$7.8MIdentification of non-coding RNAs to therapeutically target undruggable pathways in metastatic lung adenocarcinoma and squamous cell carcinomaR35CA197452 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI FLORES, ELSA R · 2016 to 2022
$6.4MComputational and Experimental Modeling of Alternative PolyadenylationR01CA193466 · NCI · UNIVERSITY OF CALIFORNIA-IRVINE · PI LI, WEI · 2016 to 2025
$3.3MComputational and Experimental Modeling of Epigenetic DNA MethylationR01HG007538 · NHGRI · UNIVERSITY OF CALIFORNIA-IRVINE · PI LI, WEI · 2014 to 2018
$1.9MRole of the Histone Methyltransferase MLL4 in MedulloblastomaR01CA207109 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI LEE, MIN GYU · 2017 to 2021
$1.9MRole of the Histone Modifier KDM2A in Lung CancerR01CA207098 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI LEE, MIN GYU · 2017 to 2021
$1.8MSYNAPTIC ORIGINS OF CEREBELLAR DISEASER01NS089664 · NINDS · BAYLOR COLLEGE OF MEDICINE · PI SILLITOE, ROY VINCENT · 2014 to 2018
$1.7MRole of S-nitrosylation in TransdifferentiationR01HL133254 · NHLBI · METHODIST HOSPITAL RESEARCH INSTITUTE · PI CHEN, KAIFU, COOKE, JOHN P · 2018 to 2021
$1.6MRole of the Histone demethylase JARID1d in Epigenetic Events of Prostate CancerR01CA157919 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI LEE, MIN GYU · 2011 to 2015
$1.5MStudy of a Novel Deubiquitylase in MedulloblastomaR01NS079715 · NINDS · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI GOPALAKRISHNAN, VIDYA · 2012 to 2015
$1.4MNCI NIH HHS P30 CA016672NCI NIH HHS R01 CA157919NCI NIH HHS R01 CA193466NCI NIH HHS R01 CA207098NCI NIH HHS R01 CA207109NCI NIH HHS R35 CA197452NCI NIH HHS R35 CA197569NHGRI NIH HHS R01 HG007538NHLBI NIH HHS R01 HL133254NICHD NIH HHS U54 HD083092NINDS NIH HHS R01 NS079715NINDS NIH HHS R01 NS089664NINDS NIH HHS R03 NS077021
Abstract
Super-enhancers are large clusters of enhancers that activate gene expression. Broad trimethyl histone H3 lysine 4 (H3K4me3) often defines active tumor suppressor genes. However, how these epigenomic signatures are regulated for tumor suppression is little understood. Here we show that brain-specific knockout of the H3K4 methyltransferase MLL4 (a COMPASS-like enzyme, also known as KMT2D) in mice spontaneously induces medulloblastoma. Mll4 loss upregulates oncogenic Ras and Notch pathways while downregulating neuronal gene expression programs. MLL4 enhances DNMT3A-catalyzed DNA methylation and SIRT1/BCL6-mediated H4K16 deacetylation, which antagonize expression of Ras activators and Notch pathway components, respectively. Notably, Mll4 loss downregulates tumor suppressor genes (e.g., Dnmt3a and Bcl6) by diminishing broad H3K4me3 and super-enhancers and also causes widespread impairment of these epigenomic signatures during medulloblastoma genesis. These findings suggest an anti-tumor role for super-enhancers and provide a unique tumor-suppressive mechanism in which MLL4 is necessary to maintain broad H3K4me3 and super-enhancers at tumor suppressor genes.
Indexed as
DNA MethylationGenes, Tumor SuppressorOncogenesProtein Processing, Post-TranslationalAcetylationAnimalsCell ProliferationCerebellar NeoplasmsDNA (Cytosine-5-)-MethyltransferasesDNA Methyltransferase 3AGene Expression Regulation, NeoplasticGenes, rasHistone-Lysine N-MethyltransferaseLysineMedulloblastomaMice, KnockoutBcl6 protein, mouseDNA (Cytosine-5-)-MethyltransferasesDNA Methyltransferase 3ADnmt3a protein, mouseHistone-Lysine N-MethyltransferaseLysineMLL4 protein, mouseProto-Oncogene Proteins c-bcl-6Receptors, NotchSirt1 protein, mouseSirtuin 1broad H3K4me3DNA methylationepigeneticsH4K16 deacetylationhistone methyltransferaseMLL4NotchRassuper-enhancerstumor suppressor
Identifiers
What OpenQuestion holds
Textmetadata
LicenceTDM
Read underepoch 390
Registered trials
None linked
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.