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BET Bromodomains Mediate Transcriptional Pause Release in Heart Failure
Open accessAbstract
Heart failure (HF) is driven by the interplay between regulatory transcription factors and dynamic alterations in chromatin structure. Pathologic gene transactivation in HF is associated with recruitment of histone acetyl-transferases and local chromatin hyperacetylation. We therefore assessed the role of acetyl-lysine reader proteins, or bromodomains, in HF. Using a chemical genetic approach, we establish a central role for BET family bromodomain proteins in gene control during HF pathogenesis. BET inhibition potently suppresses cardiomyocyte hypertrophy in vitro and pathologic cardiac remodeling in vivo. Integrative transcriptional and epigenomic analyses reveal that BET proteins function mechanistically as pause-release factors critical to expression of genes that are central to HF pathogenesis and relevant to the pathobiology of failing human hearts. This study implicates epigenetic readers as essential effectors of transcriptional pause release during HF pathogenesis and identifies BET coactivator proteins as therapeutic targets in the heart.
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“BET inhibition exerted a strong protective effect on left ventricular ejection fraction (Fig. 1B)4,6-10.”
From Chromatin remodelling drives immune cell–fibroblast communication in heart failure (2024) · cites this paper as [6]
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“As BET proteins are transcriptional co-activators and their inhibition is associated with protection in heart failure models6-8”
From Chromatin remodelling drives immune cell–fibroblast communication in heart failure (2024) · cites this paper as [6]
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“model of cardiac pressure overload, which provides focal hemodynamic stress to the heart and recapitulates several cardinal aspects of pathologic hypertrophy and HF in humans (Rockman et al., 1991).”
RetractedSubramanian, A., Tamayo, P., Mootha, V. K., Mukherjee, S., Ebert, B. L., Gillette, M. A., Paulovich, A., Pomeroy, S. L., Golub, T. R., Lander, E. S., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0506580102 · Cited by 53,625 · cited 1×
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Ultrafast and memory-efficient alignment of short DNA sequences to the human genome.
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Model-based Analysis of ChIP-Seq (MACS)
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“The pathologic nature of this process has been validated in large epidemiologic studies, which demonstrate that the presence of chronic cardiac hypertrophy is a robust predictor of subsequent HF and death (Hill and Olson, 2008; Levy et al., 1990).”
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 · cited 4×
“We and others have utilized this chemical genetic tool to probe BET function in a number of developmental and disease contexts, such as cancer (Delmore et al., 2011; Filippakopoulos et al., 2010), HIV infection (Banerjee et al.”
InfluentialSelf-citationSelective Inhibition of Tumor Oncogenes by Disruption of Super-Enhancers
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“Furthermore, the very recent discovery of asymmetrically loaded BRD4 on a critical subset of state-specific enhancers termed superenhancers (Lovén et al., 2013) raises the possibility that such superenhancers might also be active in the stressed myocardium and contribute to BET target specificity.”
Self-citationBET Bromodomain Inhibition as a Therapeutic Strategy to Target c-Myc
Delmore, J. E., Issa, G. C., Lemieux, M. E., Rahl, P. B., Shi, J., Jacobs, H. M., Kastritis, E., Gilpatrick, T., Paranal, R. M., Qi, J., et al. (2011) · Cell · doi:10.1016/j.cell.2011.08.017 · Cited by 2,888 · cited 4×
“Prior studies from our laboratory and others have implicated BET bromodomains in neoplastic MYC transcription in hematopoietic tumors (Delmore et al., 2011; Zuber et al., 2011).”
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“Specifically, we studied the Broad Institute Molecular Signatures Database C3 motif gene sets (Xie et al., 2005), as well as three functional, in vivo signatures of CMspecific transcriptional effectors: Calcineurin-NFAT (Bousette et al.”
RNAi screen identifies Brd4 as a therapeutic target in acute myeloid leukaemia
Zuber, J., Shi, J., Wang, E., Rappaport, A. R., Herrmann, H., Sison, E. A., Magoon, D., Qi, J., Blatt, K., Wunderlich, M., et al. (2011) · Nature · doi:10.1038/nature10334 · Cited by 1,870 · cited 2×
“Prior studies from our laboratory and others have implicated BET bromodomains in neoplastic MYC transcription in hematopoietic tumors (Delmore et al., 2011; Zuber et al., 2011).”
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Phthalimide conjugation as a strategy for in vivo target protein degradation
Winter, G. E., Buckley, D. L., Paulk, J., Roberts, J. M., Souza, A., Dhe-Paganon, S., & Bradner, J. E. (2015) · Science · doi:10.1126/science.aab1433 · Cited by 1,760
Self-citationTargeting bromodomains: epigenetic readers of lysine acetylation
Filippakopoulos, P., & Knapp, S. (2014) · Nature Reviews Drug Discovery · doi:10.1038/nrd4286 · Cited by 1,298
The dTAG system for immediate and target-specific protein degradation
Nabet, B., Roberts, J. M., Buckley, D. L., Paulk, J., Dastjerdi, S., Yang, A., Leggett, A. L., Erb, M. A., Lawlor, M. A., Souza, A., et al. (2018) · Nature Chemical Biology · doi:10.1038/s41589-018-0021-8 · Cited by 1,118
Self-citationThe Mechanisms behind the Therapeutic Activity of BET Bromodomain Inhibition
Shi, J., & Vakoc, C. R. (2014) · Molecular Cell · doi:10.1016/j.molcel.2014.05.016 · Cited by 888
“Gene expression analysis of JQ1-treated cardiomyocytes identified systematic downregulation of NFkB target genes, further suggesting that BET inhibitors can attenuate NFkB function (Anand et al., 2013).”
BackgroundInfluentialNF-κB Directs Dynamic Super Enhancer Formation in Inflammation and Atherogenesis
Brown, J. D., Lin, C. Y., Duan, Q., Griffin, G., Federation, A. J., Paranal, R. M., Bair, S., Newton, G., Lichtman, A. H., Kung, A. L., et al. (2014) · Molecular Cell · doi:10.1016/j.molcel.2014.08.024 · Cited by 614
Self-citationPromoter-proximal pausing of RNA polymerase II: a nexus of gene regulationPreprint
Core, L. J., & Adelman, K. (2019) · Genes & Development · doi:10.1101/gad.325142.119 · Cited by 611
“In particular, it was noted in gene expression analysis that BET-inhibition caused significant up-regulation of HEXIM1, a central component of the inactive 7SK complex, which would cause cellular sequestration of PTEFb (Anand et al. 2013).”
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“Using inhibitors of the bromodomain and extra-terminal domain (BET) family, we and others have suggested a contributory role for BRD4 in release of promoter-proximally paused RNA Polymerase II (Pol II) for productive transcription elongation (Anand et al., 2013; Lovén et al., 2013).”
Self-citationBrd4 and JMJD6-Associated Anti-Pause Enhancers in Regulation of Transcriptional Pause Release
Liu, W., Ma, Q., Wong, K., Li, W., Ohgi, K., Zhang, J., Aggarwal, A. K., & Rosenfeld, M. G. (2013) · Cell · doi:10.1016/j.cell.2013.10.056 · Cited by 421
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“Administration of JQ1 improves cardiac function in preestablished heart failure or myocardial infarction mice.(46,278) Thus, BRD4 inhibitor JQ1 will be used as a drug for the clinical treatment of heart failure and myocardial infarction in future.”
BackgroundChanges in m6A RNA Methylation Contribute to Heart Failure Progression by Modulating Translation
Berulava, T., Buchholz, E., Vakhtang, E., Peña, T., Islam, R., Lbik, D., Mohamed, B. A., Renner, A., von Lewinski, D., Sacherer, M., et al. (2019) · European Journal of Heart Failure · doi:10.1002/ejhf.1672 · Cited by 326
Drug Discovery Targeting Bromodomain-Containing Protein 4
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Dynamic DNA methylation orchestrates cardiomyocyte development, maturation and disease
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BRD4 assists elongation of both coding and enhancer RNAs by interacting with acetylated histones
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Targeting Age-Related Pathways in Heart Failure
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“Introduction Protein–protein interactions (PPIs) are potential drug targets for a broad range of therapeutic areas, such as oncology [1,2 ,3,4 ,5], immune-checkpoints for cancer immunotherapy [6], tropical infectious diseases [7 ], neurological disorders [8], heart failure [9] and inflammation”
BackgroundDuan, Q., McMahon, S., Anand, P., Shah, H., Thomas, S., Salunga, H. T., Huang, Y., Zhang, R., Sahadevan, A., Lemieux, M. E., et al. (2017) · Science Translational Medicine · doi:10.1126/scitranslmed.aah5084 · Cited by 262
“Furthermore, JQ1 does not cause major changes in cardiac structure or function inmice subject to sham surgery (31).”
BackgroundMethodResultInfluentialSelf-citationGilsbach, R., Schwaderer, M., Preißl, S., Grüning, B. A., Kranzhöfer, D., Schneider, P., Nührenberg, T. G., Mulero‐Navarro, S., Weichenhan, D., Braun, C., et al. (2018) · Nature Communications · doi:10.1038/s41467-017-02762-z · Cited by 251
Bromodomain biology and drug discovery
Zaware, N., & Zhou, M. (2019) · Nature Structural & Molecular Biology · doi:10.1038/s41594-019-0309-8 · Cited by 264
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Gillette, T. G., & Hill, J. A. (2015) · Circulation Research · doi:10.1161/circresaha.116.303630 · Cited by 260
A transcriptional switch governs fibroblast activation in heart disease
Alexanian, M., Przytycki, P. F., Micheletti, R., Padmanabhan, A., Ye, L., Travers, J. G., Gonzalez-Teran, B., Silva, A. C., Duan, Q., Ranade, S. S., et al. (2021) · Nature · doi:10.1038/s41586-021-03674-1 · Cited by 238
Self-citationBromodomains: Structure, function and pharmacology of inhibition
Ferri, E., Petosa, C., & McKenna, C. E. (2015) · Biochemical Pharmacology · doi:10.1016/j.bcp.2015.12.005 · Cited by 249
BET inhibition blocks inflammation-induced cardiac dysfunction and SARS-CoV-2 infection
Mills, R. J., Humphrey, S. J., Fortuna, P. R. J., Lor, M., Foster, S. R., Quaife-Ryan, G. A., Johnston, R. L., Dumenil, T. D., Bishop, C., Rudraraju, R., et al. (2021) · Cell · doi:10.1016/j.cell.2021.03.026 · Cited by 229
“, 2019), in experimental models of pressure overload and myocardial infarction-induced HF (Anand et al., 2013), and in genetic cardiomyopathies (Antolic et al.”
Inhibition of BET bromodomains as a therapeutic strategy for cancer drug discovery
Fu, L., Tian, M., Li, X., Li, J., Huang, J. M., Ouyang, L., Zhang, Y., & Liu, B. (2015) · Oncotarget · doi:10.18632/oncotarget.3551 · Cited by 231
“BRD proteins bind to acetylated lysine (Kac) and thus acting as readers of lysine acetylation state; HATs effect lysine acetylation acting as writers; HDACs and SIRTs remove acetyl groups as erasers [9].”
BackgroundKleppe, M., Koche, R., Zou, L., van Galen, P., Hill, C. E., Dong, L., De Groote, S., Papalexi, E., Hanasoge Somasundara, A. V., Cordner, K., et al. (2018) · Cancer Cell · doi:10.1016/j.ccell.2017.11.009 · Cited by 279
“Recent studies have suggested an important role for the histone lysine reader BRD4 in mediating pathologic inflammation in different contexts, including sepsis, pulmonary fibrosis, and heart failure (Anand et al., 2013; Brown et al., 2014; Nicodeme et al., 2010; Tang et al., 2013).”
BackgroundSelf-citationDi Micco, R., Fontanals-Cirera, B., Low, V., Ntziachristos, P., Yuen, S. K., Lovell, C. D., Dolgalev, I., Yonekubo, Y., Zhang, G., Rusinova, E., et al. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.08.055 · Cited by 217
“BRD4 has been described as a Pol II pause release factor necessary for gene expression (Anand et al., 2013).”
BackgroundThe bromodomain: From epigenome reader to druggable target
Sánchez, R., Meslamani, J. E., & Zhou, M. (2014) · Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms · doi:10.1016/j.bbagrm.2014.03.011 · Cited by 201
“There are multiple disease areas in which BrD inhibitors have been used [19, 46]; mainly cancer [17], HIV/AIDS [18], cardiovascular disease [49, 79], and inflammation [51].”
BackgroundDynamic Chromatin Targeting of BRD4 Stimulates Cardiac Fibroblast Activation
Stratton, M. S., Bagchi, R. A., Felisbino, M. B., Hirsch, R. A., Smith, H. E., Riching, A. S., Enyart, B. Y., Koch, K. A., Cavasin, M. A., Alexanian, M., et al. (2019) · Circulation Research · doi:10.1161/circresaha.119.315125 · Cited by 179
Self-citationTargeting Cancer Cells with BET Bromodomain InhibitorsPreprint
Xu, Y., & Vakoc, C. R. (2017) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a026674 · Cited by 187
“Transcriptome-level studies have revealed that BET inhibitors suppress hundreds of genes in each cell type (Anand et al. 2013; Chapuy et al. 2013; Lovén et al. 2013; Asangani et al. 2014).”
BackgroundInfluentialGenomic analyses implicate noncoding de novo variants in congenital heart disease
Richter, F., Morton, S. U., Kim, S. W., Kitaygorodsky, A., Wasson, L. K., Chen, K., Zhou, J., Qi, H., Patel, N., DePalma, S. R., et al. (2020) · Nature Genetics · doi:10.1038/s41588-020-0652-z · Cited by 180
Therapeutic targets for cardiac fibrosis: from old school to next-gen
Travers, J. G., Tharp, C. A., Rubino, M., & McKinsey, T. A. (2022) · Journal of Clinical Investigation · doi:10.1172/jci148554 · Cited by 179
“One of the most highly regulated elements was a large enhancer downstream of the gene encoding Meox1, a homeodomain-containing transcription factor whose expression was highly upregulated in myofibroblasts after TAC and suppressed by JQ1.”
BackgroundInfluentialEpigenetic modifications and noncoding RNAs in cardiac hypertrophy and failure
Greco, C. M., & Condorelli, G. (2015) · Nature Reviews Cardiology · doi:10.1038/nrcardio.2015.71 · Cited by 162
Epigenetic drug discovery: breaking through the immune barrier
Tough, D. F., Tak, P. P., Tarakhovsky, A., & Prinjha, R. K. (2016) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2016.185 · Cited by 163
MYC protein stability is negatively regulated by BRD4
Devaiah, B. N., Mu, J., Akman, B., Uppal, S., Weissman, J. D., Cheng, D., Baranello, L., Nie, Z., Levens, D., & Singer, D. S. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1919507117 · Cited by 159
“Since MYC degradation is necessary for transcriptional pause release (9), we speculate that BRD4-mediated degradation of MYC effects pause release (49, 50) and the accompanying loss of total MYC levels is compensated by BRD4-mediated activation of MYC transcription.”
BackgroundEpigenetic mechanisms of importance for drug treatment
Ivanov, M., Barragán, I., & Ingelman‐Sundberg, M. (2014) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2014.05.004 · Cited by 161
BET Epigenetic Reader Proteins in Cardiovascular Transcriptional Programs
Borck, P. C., Guo, L., & Plutzky, J. (2020) · Circulation Research · doi:10.1161/circresaha.120.315929 · Cited by 155
Self-citationReady, pause, go: regulation of RNA polymerase II pausing and release by cellular signaling pathways
Liu, X., Kraus, W. L., & Bai, X. (2015) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2015.07.003 · Cited by 163
Epigenetics in Cardiac Hypertrophy and Heart Failure
Liu, C., & Tang, W. H. W. (2019) · JACC Basic to Translational Science · doi:10.1016/j.jacbts.2019.05.011 · Cited by 150
“Studies on modulating the function of bromodomain (BET) proteins, an acetylated-lysine binding protein and an epigenetic reader, have suggested that chromatin structure and organization are important in regulating the kinetics of gene expression in failing hearts (39,40).”
BackgroundBeating the odds: BETs in disease
Wang, C., & Filippakopoulos, P. (2015) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2015.06.002 · Cited by 156
Epigenetic polypharmacology: from combination therapy to multitargeted drugs
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Epigenetic Changes in Diabetes and Cardiovascular Risk
Keating, S. T., Plutzky, J., & El-Osta, A. (2016) · Circulation Research · doi:10.1161/circresaha.116.306819 · Cited by 139
“Of note, BETs use a different set of targets to direct transcriptional programs in cardiomyocytes, where BET inhibition blocks cardiac remodeling in response to transaortic constriction and pressure overload.(148)”
Self-citationLehmann, L., Jebessa, Z. H., Kreußer, M. M., Horsch, A. K., He, T., Kronlage, M., Dewenter, M., Sramek, V., Oehl, U., Krebs-Haupenthal, J., et al. (2017) · Nature Medicine · doi:10.1038/nm.4452 · Cited by 138
The impact of epigenetics on cardiovascular disease
Prasher, D., Greenway, S. C., & Singh, R. B. (2019) · Biochemistry and Cell Biology · doi:10.1139/bcb-2019-0045 · Cited by 143
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Epigenetics and inheritance of phenotype variation in livestock
Triantaphyllopoulos, K. A., Ikonomopoulos, I., & Bannister, A. J. (2016) · Epigenetics & Chromatin · doi:10.1186/s13072-016-0081-5 · Cited by 141
“For instance, BRD4 inhibitors effectively suppress murine cardiomyocyte hypertrophy, in vitro and pathological cardiac remodelling, in vivo [187].”
BackgroundChromatin remodelling drives immune cell–fibroblast communication in heart failure
Alexanian, M., Padmanabhan, A., Nishino, T., Travers, J. G., Ye, L., Pelonero, A., Lee, C. Y., Sadagopan, N., Huang, Y., Auclair, K., et al. (2024) · Nature · doi:10.1038/s41586-024-08085-6 · Cited by 140
Self-citationPause & go: from the discovery of RNA polymerase pausing to its functional implications
Mayer, A., Landry, H. M., & Churchman, L. S. (2017) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2017.03.002 · Cited by 125
“Promoter-proximal pausing and aberrant pause release have been implicated in various human pathologies [117 ] such as in c-Myc driven cancers [25,118] and cardiac hypertrophy [119], and also plays a role in inflammatory responses [120], as well as in development [11,121].”
BackgroundThe Bromodomain: A New Target in Emerging Epigenetic Medicine
Smith, S. G., & Zhou, M. (2015) · ACS Chemical Biology · doi:10.1021/acschembio.5b00831 · Cited by 130
Bromodomains and Their Pharmacological Inhibitors
Gallenkamp, D., Gelato, K. A., Haendler, B., & Weinmann, H. (2014) · ChemMedChem · doi:10.1002/cmdc.201300434 · Cited by 129
BRD4 directs hematopoietic stem cell development and modulates macrophage inflammatory responses
Dey, A., Yang, W., Gégonne, A., Nishiyama, A., Pan, R., Yagi, R., Grinberg, A., Finkelman, F. D., Pfeifer, K. E., Zhu, J., et al. (2019) · The EMBO Journal · doi:10.15252/embj.2018100293 · Cited by 128
“…related diseases, including LPS-induced sepsis, EAE-based neuroinflammation, diabetes, and cardio-vascular diseases (Nicodeme et al , 2010; Bandukwala et al , 2012; Anand et al , 2013; Belkina et al , 2013; Mele et al , 2013; Brown Jonathan et al , 2014; Fu et al , 2014; Duan et al , 2017).”
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“JQ1 mitigated bleomycin-induced murine lung fibrosis [13] and pressure overload-induced cardiac fibrosis [14].”
BackgroundTargeting histone acetylation in pulmonary hypertension and right ventricular hypertrophy
Chelladurai, P., Boucherat, O., Stenmark, K. R., Kracht, M., Seeger, W., Bauer, U., Bonnet, S., & Pullamsetti, S. S. (2019) · British Journal of Pharmacology · doi:10.1111/bph.14932 · Cited by 117
“Although substantial differences exist between the right and left ventricles including embryological origin, chamber geometry and response to therapies, the beneficial effects of BET inhibition on the RV are consistent with studies reporting that treatment with JQ1 preserves LV function following transverse aortic con…”
ResultThe Functions of BET Proteins in Gene Transcription of Biology and Diseases
Cheung, K. L., Kim, C., & Zhou, M. (2021) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2021.728777 · Cited by 115
Inhibitors of bromodomain and extra‐terminal proteins for treating multiple human diseases
Kulikowski, E., Rakai, B. D., & Wong, N. C. W. (2020) · Medicinal Research Reviews · doi:10.1002/med.21730 · Cited by 109
“coactivator of pathologic gene transactivation in these models.(53) Mirroring what occurs in vascular endothelial”
BackgroundResultInfluentialSystemic Aging Fuels Heart Failure: Molecular Mechanisms and Therapeutic Avenues
Fang, Z., Raza, U., Song, J., Lu, J., Yao, S., Liu, X., Zhang, W., & Li, S. (2024) · ESC Heart Failure · doi:10.1002/ehf2.14947 · Cited by 117
“250 In principle, BET inhibition blocks NF-κ B and TGF-β -mediated in-fl ammatory and pro fi brotic gene networks, 251 suggesting a potential therapeutic avenue for protection against cardiac aging phenotypes and age-related chronic HF. Resveratrol, a SIRT1 inducer, potentially alleviates oxidative…”
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Role of the Epigenome in Heart Failure
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Functions of BET proteins in erythroid gene expression
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Bromodomain and Extraterminal Proteins as Novel Epigenetic Targets for Renal Diseases
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“NF-κB activation is a response to a variety of extracellular stimuli, and inflammationrelated NF-κB signaling pathways are essential in the development of atherosclerosis [38].”
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“4 For instance, RNA N6-adenosine methylation has been shown to have a critical role in the development of cardiac remodeling.”
BackgroundBET bromodomain proteins regulate enhancer function during adipogenesis
Brown, J. D., Feldman, Z. B., Doherty, S. P., Reyes, J. M., Rahl, P. B., Lin, C. Y., Sheng, Q., Duan, Q., Alexander Joel Federation, Kung, A. L., et al. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1711155115 · Cited by 90
“Recently, a distinct role for BETs has been described in transcription control of dynamic, stimulus-coupled cell state transitions in heart failure and inflammation (18, 19).”
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Small-Molecule Targeting of BET Proteins in Cancer
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Signal-Dependent Recruitment of BRD4 to Cardiomyocyte Super-Enhancers Is Suppressed by a MicroRNA
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BackgroundInfluentialBET bromodomain inhibition attenuates cardiac phenotype in myocyte-specific lamin A/C–deficient mice
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“The findings in LMNA-DCM mice are in agreement with previous data on the profibrotic effects of BRD4 and the beneficial effects of JQ1, a first-in-class paninhibitor of BET bromodomain proteins, on attenuation of myocardial fibrosis and cardiac dysfunction in pressure overload and myocardial infarction mouse models (3…”
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Epigenomes in Cardiovascular Disease
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“…BRD4 (bromodomain-containing protein 4), whose inhibition with the small molecule JQ1 prevents hypertrophy and associated transcriptional chang-es 28,29 and whose pharmacological inhibition reverses some of the fibrotic and deleterious structural remodeling in the wake of infarction or pressure…”
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“[107] BRD4 has also been reported to be partially responsible for the expression of genes that cause heart failure.[108]”
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“In line with its role in recruiting PTEFb for stimulation of transcriptional elongation, Brd4 has been shown to be indispensable for cell proliferation [47–49], as well as the integration and transcription of HIV-1 [65– 70], inflammatory response [8, 71, 72], cardiac hypertrophy [73, 74], and DNA damage repair [75, 76…”
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CXCL8 histone H3 acetylation is dysfunctional in airway smooth muscle in asthma: regulation by BET
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Platelet and Erythrocyte Membranes Coassembled Biomimetic Nanoparticles for Heart Failure Treatment
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Targeting BET bromodomain proteins in cancer: The example of lymphomas
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Epigenetic regulation of cardiac fibrosis
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“JQ1 was shown to block interstitial cardiac fibrosis and myocyte hypertrophy in mice subjected to TAC [94, 95].”
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“Previous studies have indicated a central role for BET proteins in gene control during heart failure pathogenesis (11,12).”
Metadata
- Authors
- Anand, P., Brown, J. D., Lin, C. Y., Qi, J., Zhang, R., Artero, P. C., Alaiti, M. A., Bullard, J., Alazem, K., Margulies, K. B., Cappola, T. P., Lemieux, M., Plutzky, J., Bradner, J. E., & Haldar, S. M.
- Affiliations
- University Hospitals of Cleveland (US)
- Brigham and Women's Hospital (US)
- Dana-Farber Cancer Institute (US)
- University of Pennsylvania (US)
- Harvard University (US)
- Corresponding author
- Bradner, James E.
- Haldar, Saptarsi M.
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2013-08
- Volume
- 154
- Issue
- 3
- Pages
- 569-582
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC4090947
- OpenAlex
- W2154924534
- Cited by
- 406
- References
- 63
- Citations by year
- 2026: 21 · 2025: 26 · 2024: 18 · 2023: 25 · 2022: 25 · 2021: 36 · 2020: 49 · 2019: 33 · 2018: 28 · 2017: 29 · 2016: 36 · 2015: 42 · 2014: 30 · 2013: 6
- FWCI
- 17.01
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Wellcome Trust
- National Heart, Lung, and Blood Institute (T32HL105338, K08HL105678, K08HL086614, R01HL105993, P01HL048743)
- National Cancer Institute (K08CA128972)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK093821)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Degradation and Inhibitors
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
- Keywords
- heart failure, BET proteins, chromatin acetylation, histone acetyltransferase, cardiac remodeling, cardiomyocyte hypertrophy, epigenetic reader protein, BET inhibition, gene expression regulation, chemical genetics
- MeSH terms
- Animals, Chromatin, Disease Models, Animal, Heart, Cardiomegaly, Heart Failure, Humans, Mice, Inbred C57BL, Transcription Factors, Transcription, Genetic, Protein Structure, Tertiary, Myocytes, Cardiac, Epigenesis, Genetic, Mice, Rats, Transcriptome
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