Cited by 2,961Protein Degradation and InhibitorsChromatin Remodeling and CancerGenomics and Chromatin Dynamics

The DOI matches its Crossref record; 86 of the 86 references it cites were found in a registry or an index.

Selective Inhibition of Tumor Oncogenes by Disruption of Super-Enhancers

Open access

Lovén, Jakob, Hoke, Heather A., Lin, Charles Y., Lau, Ashley, Orlando, David A., Vakoc, Christopher R., Bradner, James E., Lee, Tong Ihn, Young, Richard A.·2013·Cell

DOI 10.1016/j.cell.2013.03.036PMC PMC3760967

Open this paper in CoChat — free account Open PDF

Abstract

Chromatin regulators have become attractive targets for cancer therapy, but it is unclear why inhibition of these ubiquitous regulators should have gene-specific effects in tumor cells. Here, we investigate how inhibition of the widely expressed transcriptional coactivator BRD4 leads to selective inhibition of the MYC oncogene in multiple myeloma (MM). BRD4 and Mediator were found to co-occupy thousands of enhancers associated with active genes. They also co-occupied a small set of exceptionally large super-enhancers associated with genes that feature prominently in MM biology, including the MYC oncogene. Treatment of MM tumor cells with the BET-bromodomain inhibitor JQ1 led to preferential loss of BRD4 at super-enhancers and consequent transcription elongation defects that preferentially impacted genes with super-enhancers, including MYC. Super-enhancers were found at key oncogenic drivers in many other tumor cells. These observations have implications for the discovery of cancer therapeutics directed at components of super-enhancers in diverse tumor types.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Integrity signals

Registry

Crossref · 10.1016/j.cell.2013.03.036

Cites

86 of 86 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Ultrafast and memory-efficient alignment of short DNA sequences to the human genome.
Langmead, B., Trapnell, C., Pop, M., & Salzberg, S. L. (2009) · Genome Biology · doi:10.1186/gb-2009-10-3-r25 · Cited by 21,849
Model-based Analysis of ChIP-Seq (MACS)
Zhang, Y., Liu, T., Meyer, C. A., Eeckhoute, J., Johnson, D. S., Bernstein, B. E., Nusbaum, C., Myers, R. M., Brown, M., Li, W., et al. (2008) · Genome Biology · doi:10.1186/gb-2008-9-9-r137 · Cited by 18,386
Topological domains in mammalian genomes identified by analysis of chromatin interactions
Dixon, J. R., Selvaraj, S., Yue, F., Kim, A., Li, Y., Shen, Y., Hu, M., Liu, J. S., & Ren, B. (2012) · Nature · doi:10.1038/nature11082 · Cited by 6,829
NCBI reference sequences (RefSeq): a curated non-redundant sequence database of genomes, transcripts and proteins
Pruitt, K. D., Tatusova, T. A., & Maglott, D. R. (2006) · Nucleic Acids Research · doi:10.1093/nar/gkl842 · Cited by 4,441
Histone H3K27ac separates active from poised enhancers and predicts developmental state
Creyghton, M. P., Cheng, A. W., Welstead, G. G., Kooistra, T., Carey, B. W., Steine, E. J., Hanna, J., Lodato, M. A., Frampton, G. M., Sharp, P. A., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1016071107 · Cited by 4,302
Self-citation
Selective inhibition of BET bromodomains
Filippakopoulos, P., Qi, J., Picaud, S., Shen, Y., Smith, W. B., Fedorov, O., Morse, E. M., Keates, T., Hickman, T. T., Felletar, I., et al. (2010) · Nature · doi:10.1038/nature09504 · Cited by 4,262
Self-citation
Master Transcription Factors and Mediator Establish Super-Enhancers at Key Cell Identity Genes
Whyte, W. A., Orlando, D. A., Hnisz, D., Abraham, B. J., Lin, C. Y., Kagey, M. H., Rahl, P. B., Lee, T. I., & Young, R. A. (2013) · Cell · doi:10.1016/j.cell.2013.03.035 · Cited by 4,143
Self-citation
The landscape of somatic copy-number alteration across human cancers
Beroukhim, R., Mermel, C. H., Porter, D., Wei, G., Raychaudhuri, S., Donovan, J., Barretina, J., Boehm, J. S., Dobson, J., Urashima, M., et al. (2010) · Nature · doi:10.1038/nature08822 · Cited by 4,017
Epigenetics in Cancer
Esteller, M. (2008) · New England Journal of Medicine · doi:10.1056/nejmra072067 · Cited by 3,767
Integrative annotation of human large intergenic noncoding RNAs reveals global properties and specific subclassesPreprint
Cabili, M. N., Trapnell, C., Goff, L. A., Koziol, M. J., Tazón‐Vega, B., Regev, A., & Rinn, J. L. (2011) · Genes & Development · doi:10.1101/gad.17446611 · Cited by 3,551

Flagged first, then by citations

Show all 86 references

Sorted by citations

Items 701–800 of 1,008

Pancreatic Cancer Patient Survival Correlates with DNA Methylation of Pancreas Development Genes
Thompson, M. J., Rubbi, L., Dawson, D. W., Donahue, T. R., & Pellegrini, M. A. (2015) · PLoS ONE · doi:10.1371/journal.pone.0128814 · Cited by 70
Long-range regulators of the lncRNAHOTAIRenhance its prognostic potential in breast cancer
Milevskiy, M. J. G., Al‐Ejeh, F., Saunus, J. M., Northwood, K. S., Bailey, P. J., Betts, J. A., Reed, A. E. M., Nephew, K. P., Stone, A. M., Gee, J. M. W., et al. (2016) · Human Molecular Genetics · doi:10.1093/hmg/ddw177 · Cited by 70
Superior efficacy of cotreatment with BET protein inhibitor and BCL2 or MCL1 inhibitor against AML blast progenitor cells
Fiskus, W. C., Cai, T., Dinardo, C. D., Kornblau, S. M., Borthakur, G. M., Kadia, T. M., Pemmaraju, N., Bose, P., Masárová, L., Rajapakshe, K., et al. (2019) · Blood Cancer Journal · doi:10.1038/s41408-018-0165-5 · Cited by 71
Spirits in the Material World: Enhancer RNAs in Transcriptional Regulation
Hou, T. Y., & Kraus, W. L. (2020) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2020.08.007 · Cited by 66
Enhancer Reprogramming Confers Dependence on Glycolysis and IGF Signaling in KMT2D Mutant Melanoma
Maitituoheti, M., Keung, E. Z.-Y., Tang, M., Liang, Y., Alam, H., Han, G., Singh, A. K., Raman, A. T., Terranova, C. J., Sarkar, S., et al. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.108293 · Cited by 71
The chromatin signatures of enhancers and their dynamic regulation
Barral, A., & Déjardin, J. (2023) · Nucleus · doi:10.1080/19491034.2022.2160551 · Cited by 78
MYC-driven aggressive B-cell lymphomas: biology, entity, differential diagnosis and clinical management
Cai, Q., Medeiros, L. J., Xu, X., & Young, K. H. (2015) · Oncotarget · doi:10.18632/oncotarget.5774 · Cited by 75
Brd4 bridges the transcriptional regulators, Aire and P-TEFb, to promote elongation of peripheral-tissue antigen transcripts in thymic stromal cells
Yoshida, H., Bansal, K., Schaefer, U., Chapman, T. D., Rioja, I., Proekt, I., Anderson, M. S., Prinjha, R. K., Tarakhovsky, A., Benoist, C. O., et al. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1512081112 · Cited by 68
The basal transcription machinery as a target for cancer therapy
Villicaña, C., Cruz‐Becerra, G., & Zurita, M. (2014) · Cancer Cell International · doi:10.1186/1475-2867-14-18 · Cited by 69
High-Resolution Mapping of RNA Polymerases Identifies Mechanisms of Sensitivity and Resistance to BET Inhibitors in t(8;21) AML
Zhao, Y., Liu, Q., Acharya, P., Stengel, K. R., Sheng, Q., Zhou, X., Kwak, H., Fischer, M. A., Bradner, J. E., Strickland, S. A., et al. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.07.032 · Cited by 71
Self-citation
Epigenetic Regulation in Prostate Cancer Progression
Ruggero, K., Farran-Matas, S., Martínez-Tébar, A., & Aytés, À. (2018) · Current Molecular Biology Reports · doi:10.1007/s40610-018-0095-9 · Cited by 69
Spatially constrained tandem bromodomain inhibition bolsters sustained repression of BRD4 transcriptional activity for TNBC cell growth
Ren, C., Zhang, G., Han, F., Fu, S., Cao, Y., Zhang, F., Zhang, Q., Meslamani, J. E., Xu, Y., Ji, D., et al. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1720000115 · Cited by 72
Structural and Atropisomeric Factors Governing the Selectivity of Pyrimido-benzodiazipinones as Inhibitors of Kinases and Bromodomains
Wang, J., Erazo, T., Ferguson, F. M., Buckley, D. L., Gómez, N., Muñoz‐Guardiola, P., Diéguez-Martínez, N., Deng, X., Hao, M., Massefski, W. W., et al. (2018) · ACS Chemical Biology · doi:10.1021/acschembio.7b00638 · Cited by 72
Self-citation
A transcription factor addiction in leukemia imposed by the MLL promoter sequence
Lu, B., Klingbeil, O., Tarumoto, Y., Somerville, T., Huang, Y.-H., Wei, Y.-L., Wai, D. C. C., Low, J., Milazzo, J. P., Wu, X.-L. S., et al. (2018) · Cancer Cell · doi:10.1016/j.ccell.2018.10.015 · Cited by 58
Self-citation
PAX8 activates metabolic genes via enhancer elements in Renal Cell Carcinoma
Bleu, M., Gaulis, S., Lopes, R., Sprouffske, K., Apfel, V., Holwerda, S. J. B., Pregnolato, M., Yildiz, U., Cordo’, V., Dost, A. F. M., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-11672-1 · Cited by 69
Self-citation
Analysis of an artificial zinc finger epigenetic modulator: widespread binding but limited regulation
Grimmer, M., Stolzenburg, S., Ford, E., Lister, R., Blancafort, P., & Farnham, P. (2014) · Nucleic Acids Research · doi:10.1093/nar/gku708 · Cited by 69
Activation of Oncogenic Super-Enhancers Is Coupled with DNA Repair by RAD51
Hazan, I., Monin, J., Bouwman, B. A. M., Crosetto, N., & Aqeilan, R. I. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.09.001 · Cited by 70
Targeting Super-Enhancer–Associated Oncogenes in Osteosarcoma with THZ2, a Covalent CDK7 Inhibitor
Zhang, J., Liu, W., Zou, C., Zhao, Z., Lai, Y., Shi, Z., Xie, X., Huang, G., Wang, Y., Zhang, X., et al. (2020) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-19-1418 · Cited by 69
BAF155 methylation drives metastasis by hijacking super-enhancers and subverting anti-tumor immunity
Kim, E., Liu, P., Zhang, S., Donahue, K., Wang, Y., Schehr, J. L., Wolfe, S. K., Dickerson, A., Lü, L., Rui, L., et al. (2021) · Nucleic Acids Research · doi:10.1093/nar/gkab1122 · Cited by 69
The Fra-1/AP-1 Oncoprotein: From the “Undruggable” Transcription Factor to Therapeutic Targeting
Casalino, L., Talotta, F., Cimmino, A., & Verde, P. (2022) · Cancers · doi:10.3390/cancers14061480 · Cited by 67
Kidney Cancer Is Characterized by Aberrant Methylation of Tissue-Specific Enhancers That Are Prognostic for Overall Survival
Hu, C. Y., Mohtat, D., Yu, Y., Ko, Y.-A., Shenoy, N. K., Bhattacharya, S., Izquierdo, M. C., Park, A. S. D., Giricz, O., Vallumsetla, N., et al. (2014) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-14-0494 · Cited by 69
Taking on Challenging Targets: Making MYC Druggable
Horiuchi, D., Anderton, B. N., & Goga, A. (2014) · American Society of Clinical Oncology Educational Book · doi:10.14694/edbook_am.2014.34.e497 · Cited by 67
FOXO3 Selectively Amplifies Enhancer Activity to Establish Target Gene Regulation
Eijkelenboom, A., Mokrý, M., Smits, L. M. M., Nieuwenhuis, E. E. S., & Burgering, B. M. T. (2013) · Cell Reports · doi:10.1016/j.celrep.2013.11.031 · Cited by 68
Therapeutic Targeting of BRD4 in Head Neck Squamous Cell Carcinoma
Wu, Y., Wang, Y., Diao, P., Zhang, W., Li, J., Ge, H., Song, Y., Li, Z., Wang, D., Liu, L., et al. (2019) · Theranostics · doi:10.7150/thno.31581 · Cited by 68
Epigenetic Modifiers as Potential Therapeutic Targets in Diabetic Kidney Disease
Martinez-Moreno, J. M., Fontecha‐Barriuso, M., Martín‐Sánchez, D., Guerrero‐Mauvecin, J., Gomá-Garcés, E., Fernández‐Fernández, B., Carriazo, S. M., Sánchez-Niño, M. D., Ramos, A. M., Ruiz‐Ortega, M., et al. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21114113 · Cited by 68
ARID5B as a critical downstream target of the TAL1 complex that activates the oncogenic transcriptional program and promotes T-cell leukemogenesisPreprint
Leong, W. Z., Tan, S. H., Ngoc, P. C. T., Amanda, S., Yam, A. W. Y., Liau, W., Gong, Z., Lawton, L. N., Tenen, D. G., & Sanda, T. (2017) · Genes & Development · doi:10.1101/gad.302646.117 · Cited by 67
A high‐throughput method to identify trans‐activation domains within transcription factor sequences
Arnold, C. D., Nemčko, F., Woodfin, A. R., Wienerroither, S., Vlasova, A. V., Schleiffer, A., Pagani, M., Rath, M., & Stark, A. (2018) · The EMBO Journal · doi:10.15252/embj.201798896 · Cited by 65
Not Only Mutations Matter: Molecular Picture of Acute Myeloid Leukemia Emerging from Transcriptome Studies
Handschuh, L. (2019) · Journal of Oncology · doi:10.1155/2019/7239206 · Cited by 66
Targeting BET bromodomain proteins in cancer: The example of lymphomas
Spriano, F., Stathis, A., & Bertoni, F. (2020) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2020.107631 · Cited by 70
Human placental cytotrophoblast epigenome dynamics over gestation and alterations in placental disease
Zhang, B., Kim, M. Y., Elliot, G., Zhou, Y., Zhao, G., Li, D., Lowdon, R. F., Gormley, M. J., Kapidzic, M., Robinson, J. F., et al. (2021) · Developmental Cell · doi:10.1016/j.devcel.2021.04.001 · Cited by 67
Molecular pathogenesis of multiple myeloma
Furukawa, Y., & Kikuchi, J. (2015) · International Journal of Clinical Oncology · doi:10.1007/s10147-015-0837-0 · Cited by 67
Mechanistic Analysis of the Role of Bromodomain-containing Protein 4 (BRD4) in BRD4-NUT Oncoprotein-induced Transcriptional Activation
Wang, R., & You, J. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.600759 · Cited by 71
Transformation Resistance in a Premature Aging Disorder Identifies a Tumor-Protective Function of BRD4
Fernández, P., Scaffidi, P., Markert, E. K., Lee, J.-H., Rane, S. G., & Misteli, T. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.08.069 · Cited by 66
Vulnerability of Small-Cell Lung Cancer to Apoptosis Induced by the Combination of BET Bromodomain Proteins and BCL2 Inhibitors
Lam, L. T., Lin, X., Faivre, E. J., Yang, Z., Huang, X., Wilcox, D. M., Bellin, R. J., Jin, S. S., Tahir, S. K., Mitten, M. J., et al. (2017) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-16-0459 · Cited by 67
Epe1 recruits BET family bromodomain protein Bdf2 to establish heterochromatin boundariesPreprint
Wang, J., Tadeo, X., Hou, H., Tu, P. G., Thompson, J. X., Yates, J. R., & Jia, S. (2013) · Genes & Development · doi:10.1101/gad.221010.113 · Cited by 76
MYC overexpression leads to increased chromatin interactions at super-enhancers and MYC binding sitesPreprint
See, Y. X., Chen, K., & Fullwood, M. J. (2022) · Genome Research · doi:10.1101/gr.276313.121 · Cited by 64
Exploiting epigenetic vulnerabilities for cancer therapeutics
Mair, B., Kubicek, S., & Nijman, S. M. B. (2014) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2014.01.001 · Cited by 66
Synthesis and evaluation of novel dual BRD4/HDAC inhibitors
Amemiya, S., Yamaguchi, T., Hashimoto, Y., & Noguchi‐Yachide, T. (2017) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2017.04.043 · Cited by 65
Disruption of super-enhancer-driven tumor suppressor gene RCAN1.4 expression promotes the malignancy of breast carcinoma
Deng, R., Huang, J.-H., Wang, Y., Zhou, L.-H., Wang, Z., Hu, B., Chen, Y., Yang, D., Mai, J., Li, Z., et al. (2020) · Molecular Cancer · doi:10.1186/s12943-020-01236-z · Cited by 66
Regulation of RAD51 at the Transcriptional and Functional Levels: What Prospects for Cancer Therapy?
Orhan, E., Velázquez, C., Tabet, I., Sardet, C., & Theillet, C. G. (2021) · Cancers · doi:10.3390/cancers13122930 · Cited by 68
Altered chromatin states drive cryptic transcription in aging mammalian stem cells
McCauley, B. S., Sun, L., Yu, R., Lee, M., Liu, H., Leeman, D. S., Huang, Y., Webb, A. E., & Dang, W. (2021) · Nature Aging · doi:10.1038/s43587-021-00091-x · Cited by 69
FOXA1: A Pioneer of Nuclear Receptor Action in Breast Cancer
Seachrist, D. D., Anstine, L. J., & Keri, R. (2021) · Cancers · doi:10.3390/cancers13205205 · Cited by 68
Compendium of aberrant DNA methylation and histone modifications in cancer
Hattori, N., & Ushijima, T. (2014) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2014.08.140 · Cited by 72
Proteasome inhibitors exert cytotoxicity and increase chemosensitivity via transcriptional repression of Notch1 in T-cell acute lymphoblastic leukemia
Koyama, D., Kikuchi, J., Hiraoka, N., Wada, T., Kurosawa, H., Chiba, S., & Furukawa, Y. (2013) · Leukemia · doi:10.1038/leu.2013.366 · Cited by 66
Proteolysis-Targeting Chimeras: Harnessing the Ubiquitin-Proteasome System to Induce Degradation of Specific Target Proteins
Coleman, K. G., & Crews, C. M. (2017) · Annual Review of Cancer Biology · doi:10.1146/annurev-cancerbio-030617-050430 · Cited by 72
Long non-coding RNAs in Colorectal Cancer: Progression and Future Directions
Yang, Y. P., Peng, J., Sanjun, C., & Ma, Y. (2017) · Journal of Cancer · doi:10.7150/jca.19794 · Cited by 67
Super-enhancer-guided mapping of regulatory networks controlling mouse trophoblast stem cells
Lee, B., Jang, Y. J., Kim, M., LeBlanc, L., Rhee, C., Lee, J., Beck, S. J., Shen, W., & Kim, J. (2019) · Nature Communications · doi:10.1038/s41467-019-12720-6 · Cited by 65
ATACdb: a comprehensive human chromatin accessibility database
Wang, F., Bai, X., Wang, Y., Jiang, Y., Ai, B., Zhang, Y., Liu, Y., Xu, M., Wang, Q., Han, X., et al. (2020) · Nucleic Acids Research · doi:10.1093/nar/gkaa943 · Cited by 66
Reprogramming Transcription Factors Oct4 and Sox2 Induce a BRD-Dependent Immunosuppressive Transcriptome in GBM-Propagating Cells
Ma, T., Hu, C., Lal, B., Zhou, W., Ma, Y., Ying, M., Prinos, P., Quiñones‐Hinojosa, A., Lim, M. K., Laterra, J., et al. (2021) · Cancer Research · doi:10.1158/0008-5472.can-20-2489 · Cited by 66
Aberrant activation of m6A demethylase FTO renders HIF2α low/− clear cell renal cell carcinoma sensitive to BRD9 inhibitors
Zhang, C., Chen, L., Lou, W., Su, J., Huang, J., Liu, A., Xu, Y., He, H., Gao, Y., Xu, D., et al. (2021) · Science Translational Medicine · doi:10.1126/scitranslmed.abf6045 · Cited by 66
Hepatic thyroid hormone signalling modulates glucose homeostasis through the regulation of GLP-1 production via bile acid-mediated FXR antagonism
Yan, Y., Niu, Z., Sun, C., Li, P., Shen, S., Liu, S., Wu, Y., Yun, C., Jiao, T., Jia, S., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-34258-w · Cited by 65
Histone serotonylation regulates ependymoma tumorigenesis
Chen, H., He, P., McDonald, M. F., Williamson, M. R., Varadharajan, S., Lozzi, B., Woo, J., Choi, D., Sardar, D., Huang-Hobbs, E., et al. (2024) · Nature · doi:10.1038/s41586-024-07751-z · Cited by 74
The identification of cis-regulatory elements: A review from a machine learning perspective
Li, Y., Chen, C., Kaye, A. M., & Wasserman, W. W. (2015) · Biosystems · doi:10.1016/j.biosystems.2015.10.002 · Cited by 64
T-bet Activates Th1 Genes through Mediator and the Super Elongation Complex
Hertweck, A., Evans, C. M., Eskandarpour, M., Lau, J. C. H., Oļeiņika, K., Jackson, I., Kelly, A., Ambrose, J. C., Adamson, P., Cousins, D. J., et al. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.05.054 · Cited by 72
Super enhancers at the miR-146a and miR-155 genes contribute to self-regulation of inflammation
Duan, Q., Mao, X., Xiao, Y., Liu, Z., Wang, Y., Zhou, H., Zhou, Z., Cai, J., Xia, K., Zhu, Q., et al. (2016) · Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms · doi:10.1016/j.bbagrm.2016.02.004 · Cited by 64
Repression of human and mouse brain inflammaging transcriptome by broad gene-body histone hyperacetylation
Cheng, H., Xuan, H., Green, C. D., Han, Y., Sun, N., Shen, H., McDermott, J., Bennett, D. A., Lan, F., & Han, J. J. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1800656115 · Cited by 65
Hippo-YAP signaling controls lineage differentiation of mouse embryonic stem cells through modulating the formation of super-enhancers
Sun, X., Ren, Z., Cun, Y., Zhao, C., Huang, X., Zhou, J., Hu, R., Su, X., Ji, L., Li, P., et al. (2020) · Nucleic Acids Research · doi:10.1093/nar/gkaa482 · Cited by 63
Oncogenic enhancers drive esophageal squamous cell carcinogenesis and metastasis
Ye, B., Fan, D., Xiong, W., Li, M., Yuan, J., Jiang, Q., Zhao, Y., Lin, J., Liu, J., Lv, Y., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-24813-2 · Cited by 64
Biomolecular condensates: Formation mechanisms, biological functions, and therapeutic targets
Niu, X., Zhang, L., Wu, Y., Zong, Z., Wang, B., Liu, J., Zhang, L., & Zhou, F. (2023) · MedComm · doi:10.1002/mco2.223 · Cited by 73
BET Bromodomain Blockade Mitigates Intimal Hyperplasia in Rat Carotid Arteries
Wang, B., Zhang, M., Takayama, T., Shi, X., Roenneburg, D. A., Kent, K. C., & Guo, L. (2015) · EBioMedicine · doi:10.1016/j.ebiom.2015.09.045 · Cited by 64
MYC deregulation in lymphoid tumors: molecular mechanisms, clinical consequences and therapeutic implications
Sewastianik, T., Prochorec‐Sobieszek, M., Chapuy, B., & Juszczyński, P. (2014) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2014.08.006 · Cited by 65
Epigenomics of macrophages
Gosselin, D., & Glass, C. K. (2014) · Immunological Reviews · doi:10.1111/imr.12213 · Cited by 66
High-density P300 enhancers control cell state transitions
Witte, S. J., Bradley, A., Enright, A. J., & Muljo, S. A. (2015) · BMC Genomics · doi:10.1186/s12864-015-1905-6 · Cited by 66
IER5 generates a novel hypo-phosphorylated active form of HSF1 and contributes to tumorigenesis
Asano, Y., Kawase, T., Okabe, A., Tsutsumi, S., Ichikawa, H., Tatebe, S., Kitabayashi, I., Tashiro, F., Namiki, H., Kondo, T., et al. (2016) · Scientific Reports · doi:10.1038/srep19174 · Cited by 67
Challenges and progress in interpretation of non-coding genetic variants associated with human disease
Zhu, Y., Tazearslan, C., & Suh, Y. (2017) · Experimental Biology and Medicine · doi:10.1177/1535370217713750 · Cited by 68
The BRD3 ET domain recognizes a short peptide motif through a mechanism that is conserved across chromatin remodelers and transcriptional regulators
Wai, D. C. C., Szyszka, T. N., Campbell, A. E., Kwong, C., Wilkinson‐White, L. E., Silva, A. P. G., Low, J. K. K., Kwan, A. H., Gamsjaeger, R., Chalmers, J. D., et al. (2018) · Journal of Biological Chemistry · doi:10.1074/jbc.ra117.000678 · Cited by 67
Self-citation
Targeting MYC Proteins for Tumor Therapy
Wolf, E., & Eilers, M. (2019) · Annual Review of Cancer Biology · doi:10.1146/annurev-cancerbio-030518-055826 · Cited by 65
Rapid Enhancer Remodeling and Transcription Factor Repurposing Enable High Magnitude Gene Induction upon Acute Activation of NK Cells
Sciumè, G., Mikami, Y., Jankovic, D. L., Nagashima, H., Villarino, A. V., Morrison, T. A., Yao, C., Signorella, S., Sun, H., Brooks, S. R., et al. (2020) · Immunity · doi:10.1016/j.immuni.2020.09.008 · Cited by 62
Triptolide targets super-enhancer networks in pancreatic cancer cells and cancer-associated fibroblasts
Noel, P., Hussein, S., Ng, S., Antal, C. E., Lin, W., Rodela, E., Delgado, P., Naveed, S., Downes, M., Lin, Y. C., et al. (2020) · Oncogenesis · doi:10.1038/s41389-020-00285-9 · Cited by 63
ARID1A Mutations Promote P300-Dependent Endometrial Invasion through Super-Enhancer Hyperacetylation
Wilson, M. R., Reske, J. J., Holladay, J., Neupane, S., Ngo, J., Cuthrell, N., Wegener, M., Rhodes, M., Adams, M., Sheridan, R. T. C., et al. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.108366 · Cited by 64
MyoD- and FoxO3-mediated hotspot interaction orchestrates super-enhancer activity during myogenic differentiation
Peng, X. L., So, K. K. H., He, L., Zhao, Y. F., Zhou, J., Li, Y., Yao, M., Xu, B., Zhang, S., Yao, H., et al. (2017) · Nucleic Acids Research · doi:10.1093/nar/gkx488 · Cited by 64
YAP1-Mediated Suppression of USP31 Enhances NFκB Activity to Promote Sarcomagenesis
Ye, S., Lawlor, M. A., Rivera-Reyes, A., Egolf, S., Chor, S., Pak, K., Ciotti, G. E., Lee, A. C., Marino, G. E., Shah, J., et al. (2018) · Cancer Research · doi:10.1158/0008-5472.can-17-4052 · Cited by 62
Targeting Super-Enhancers as a Therapeutic Strategy for Cancer Treatment
He, Y., Long, W., & Liu, Q. (2019) · Frontiers in Pharmacology · doi:10.3389/fphar.2019.00361 · Cited by 63
Microhomology-mediated end joining drives complex rearrangements and overexpression of MYC and PVT1 in multiple myeloma
Mikulášová, A., Ashby, C., Tytarenko, R. G., Qu, P., Rosenthal, A., Dent, J. A., Ryan, K. R., Bauer, M., Wardell, C. P., Hoering, A., et al. (2019) · Haematologica · doi:10.3324/haematol.2019.217927 · Cited by 63
The Leukemogenic TCF3-HLF Complex Rewires Enhancers Driving Cellular Identity and Self-Renewal Conferring EP300 Vulnerability
Huang, Y., Mouttet, B., Warnatz, H.-J., Risch, T., Rietmann, F., Frommelt, F., Ngo, Q. A., Dobay, M. P., Marovca, B., Jenni, S., et al. (2019) · Cancer Cell · doi:10.1016/j.ccell.2019.10.004 · Cited by 63
Molecular Mechanisms of MYCN Dysregulation in Cancers
Liu, R., Shi, P., Wang, Z., Yuan, C., & Cui, H. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2020.625332 · Cited by 67
Development of Dual ARV-825 and Nintedanib-Loaded PEGylated Nano-Liposomes for Synergistic Efficacy in Vemurafnib-Resistant Melanoma
Fu, Y., Saraswat, A. L., Wei, Z.-H., Agrawal, M. Y., Dukhande, V. V., Reznik, S. E., & Patel, K. R. (2021) · Pharmaceutics · doi:10.3390/pharmaceutics13071005 · Cited by 60
Sequence logic at enhancers governs a dual mechanism of endodermal organ fate induction by FOXA pioneer factors
Geusz, R. J., Wang, A., Lam, D. K., Vinckier, N. K., Alysandratos, K., Roberts, D. A., Wang, J., Kefalopoulou, S., Ramirez, A., Qiu, Y., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-26950-0 · Cited by 61
NUT Carcinoma: Clinicopathologic Features, Molecular Genetics and Epigenetics
Moreno, V., Saluja, K., & Piña‐Oviedo, S. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.860830 · Cited by 62
Super-enhancer-controlled positive feedback loop BRD4/ERα–RET–ERα promotes ERα-positive breast cancer
Zheng, Z., Xia, L., Hu, G.-S., Liu, J., Hu, Y.-H., Chen, Y.-J., Jia-yin, P., Zhang, W., & Liu, W. (2022) · Nucleic Acids Research · doi:10.1093/nar/gkac778 · Cited by 62
Activation of SOX2 Expression by BRD4-NUT Oncogenic Fusion Drives Neoplastic Transformation in NUT Midline Carcinoma
Wang, R., Liu, W., Helfer, C. M., Bradner, J. E., Hornick, J. L., Janicki, S. M., French, C. A., & You, J. (2014) · Cancer Research · doi:10.1158/0008-5472.can-13-2658 · Cited by 62
Self-citation
Epigenetic mechanisms of cell adhesion-mediated drug resistance in multiple myeloma
Furukawa, Y., & Kikuchi, J. (2016) · International Journal of Hematology · doi:10.1007/s12185-016-2048-5 · Cited by 65
Bromodomains in Protozoan Parasites: Evolution, Function, and Opportunities for Drug Development
Jeffers, V., Yang, C., Huang, S., & Sullivan, W. J. (2017) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.00047-16 · Cited by 61
Targeting Super-Enhancer-Driven Oncogenic Transcription by CDK7 Inhibition in Anaplastic Thyroid Carcinoma
Cao, X., Dang, L., Zheng, X., Lu, Y., Lu, Y., Ji, R., Zhang, T., Ruan, X., Zhi, J., Hou, X., et al. (2019) · Thyroid · doi:10.1089/thy.2018.0550 · Cited by 61
Chemotherapy-Induced Distal Enhancers Drive Transcriptional Programs to Maintain the Chemoresistant State in Ovarian Cancer
Shang, S., Yang, J., Jazaeri, A. A., Duval, A. J., Tufan, T., Fischer, N. L., Benamar, M., Guessous, F., Lee, I.-Y., Campbell, R. M., et al. (2019) · Cancer Research · doi:10.1158/0008-5472.can-19-0215 · Cited by 67
B-cell lymphoma mutations: improving diagnostics and enabling targeted therapies
Vaque, J. P., Martı́nez, N., Batlle‐López, A., Perez, C., Montes‐Moreno, S., Sánchez‐Beato, M., & Piris, M. A. (2014) · Haematologica · doi:10.3324/haematol.2013.096248 · Cited by 65
General mechanism of JQ1 in inhibiting various types of cancer
Jiang, G., Deng, W., Liu, Y., & Wang, C. (2020) · Molecular Medicine Reports · doi:10.3892/mmr.2020.10927 · Cited by 62
Emerging Principles in the Transcriptional Control by YAP and TAZ
Lopez-Hernandez, A., Sberna, S., & Campaner, S. (2021) · Cancers · doi:10.3390/cancers13164242 · Cited by 60
BRD4-targeting PROTAC as a unique tool to study biomolecular condensates
Shi, Y., Liao, Y., Liu, Q., Ni, Z., Zhang, Z., Shi, M., Li, P., Li, H., & Rao, Y. (2023) · Cell Discovery · doi:10.1038/s41421-023-00544-0 · Cited by 66
Characterizing heterogeneity in leukemic cells using single-cell gene expression analysis
Saadatpour, A., Guo, G., Orkin, S. H., & Yuan, G. (2014) · Genome biology · doi:10.1186/s13059-014-0525-9 · Cited by 63
Autism-like syndrome is induced by pharmacological suppression of BET proteins in young mice
Sullivan, J. M., Badimon, A., Schaefer, U., Ayata, P., Gray, J. R., Chung, C., von Schimmelmann, M. J., Zhang, F., Garton, N. S., Smithers, N. N., et al. (2015) · The Journal of Experimental Medicine · doi:10.1084/jem.20151271 · Cited by 62
NSD2 contributes to oncogenic RAS-driven transcription in lung cancer cells through long-range epigenetic activation
García-Carpizo, V., Sarmentero, J., Han, B., Graña‐Castro, O., Ruiz‐Llorente, S., Pisano, D. G., Serrano, M., Brooks, H. B., Campbell, R. M., & Barrero, M. J. (2016) · Scientific Reports · doi:10.1038/srep32952 · Cited by 62
Exploitation of Castration-Resistant Prostate Cancer Transcription Factor Dependencies by the Novel BET Inhibitor ABBV-075
Faivre, E. J., Wilcox, D. M., Li, X., Hessler, P., Torrent, M., He, W. A., Uziel, T., Albert, D. H., McDaniel, K. F., Kati, W. M., et al. (2016) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-16-0221 · Cited by 64
Lineage-specific RUNX2 super-enhancer activates MYC and promotes the development of blastic plasmacytoid dendritic cell neoplasm
Kubota, S., Tokunaga, K., Umezu, T., Yokomizo-Nakano, T., Sun, Y., Oshima, M., Tan, K., Yang, H., Kanai, A., Iwanaga, E., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-09710-z · Cited by 54
Combined treatment with CBP and BET inhibitors reverses inadvertent activation of detrimental super enhancer programs in DIPG cells
Wiese, M., Hamdan, F. H., Kubiak, K., Diederichs, C., Gielen, G. H., Nussbaumer, G., Carcaboso, A. M., Hulleman, E., Johnsen, S. A., & Kramm, C. M. (2020) · Cell Death and Disease · doi:10.1038/s41419-020-02800-7 · Cited by 60
Fast-acting chemical tools to delineate causality in transcriptional control
Jaeger, M. G., & Winter, G. E. (2021) · Molecular Cell · doi:10.1016/j.molcel.2021.02.015 · Cited by 62
The role of mutations in epigenetic regulators in myeloid malignancies
Woods, B. A., & Levine, R. L. (2014) · Immunological Reviews · doi:10.1111/imr.12246 · Cited by 63
The role of DOT1L in the maintenance of leukemia gene expression
Wang, X., Chen, C.-W. D., & Armstrong, S. A. (2016) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2016.03.015 · Cited by 60
Cofactor squelching: Artifact or fact?
Schmidt, S. F., Larsen, B. D., Loft, A., & Mandrup, S. (2016) · BioEssays · doi:10.1002/bies.201600034 · Cited by 56
Mice deficient of Myc super-enhancer region reveal differential control mechanism between normal and pathological growth
Dave, K., Sur, I., Yan, J., Zhang, J., Kaasinen, E., Zhong, F., Blaas, L., Li, X., Kharazi, S., Gustafsson, C., et al. (2017) · eLife · doi:10.7554/elife.23382 · Cited by 61

Authors: Lovén, J., Hoke, H. A., Lin, C. Y., Lau, A., Orlando, D. A., Vakoc, C. R., Bradner, J. E., Lee, T. I., & Young, R. A.
Affiliations: Whitehead Institute for Biomedical Research (US)
Dana-Farber Cancer Institute (US)
Cold Spring Harbor Laboratory (US)
Harvard University (US)
Corresponding author: Young, Richard A.
ORCID: Lin, Charles Y.
Orlando, David A.
Vakoc, Christopher R.
Bradner, James E.
Lee, Tong Ihn
Young, Richard A.
Venue: Cell
Publisher: Elsevier BV
Published: 2013-04
Volume: 153
Issue: 2
Pages: 320-334
ISSN: 0092-8674 (ISSN-L)
DOI: 10.1016/j.cell.2013.03.036
PMC: PMC3760967
OpenAlex: W1523117612
Cited by: 2,961
References: 86
Citations by year: 2026: 140 · 2025: 214 · 2024: 261 · 2023: 254 · 2022: 271 · 2021: 327 · 2020: 263 · 2019: 248 · 2018: 218 · 2017: 205 · 2016: 184 · 2015: 175 · 2014: 143 · 2013: 53
FWCI: 83.08
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 375 d)
Locations: Cell (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Cold Spring Harbor Laboratory Institutional Repository (Cold Spring Harbor Laboratory) (submittedVersion)
DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc)
Funders: National Institutes of Health (5p30ca045508-35)
National Human Genome Research Institute (HG002668, R01HG002668)
National Cancer Institute (CA146445, R01CA146445, P30-CA045508, CA45508, P30CA014051)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Degradation and Inhibitors
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
Keywords: super-enhancers, BRD4, MYC oncogene, multiple myeloma, BET inhibitors, JQ1, Mediator complex, transcriptional coactivator, transcription elongation, chromatin regulators, cancer therapy, enhancer disruption
MeSH terms: Bromodomain Containing Proteins, Antineoplastic Agents, Azepines, Chromatin, Enhancer Elements, Genetic, Humans, Multiple Myeloma, Neoplasms, Nuclear Proteins, Transcription Factors, Transcription, Genetic, Triazoles, Gene Expression Regulation, Neoplastic, Cell Cycle Proteins, Cell Line, Tumor, Genome-Wide Association Study, Mediator Complex, Transcription Elongation, Genetic

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Selective Inhibition of Tumor Oncogenes by Disruption of Super-Enhancers

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Self-check

Citations

Cites

Cited by

Related

Metadata

Record

About these checks