Cited by 417Protein Degradation and InhibitorsGenomics and Chromatin DynamicsCardiac Fibrosis and Remodeling

The DOI matches its Crossref record; 63 of the 63 references it cites were found in a registry or an index.

BET Bromodomains Mediate Transcriptional Pause Release in Heart Failure

Open access

Anand, Priti, Brown, Jonathan D., Lin, Charles Y., Qi, Jun, Zhang, Rongli, Artero, Pedro Calderon, Alaiti, M. Amer, Bullard, Jace, Alazem, Kareem, Margulies, Kenneth B., Cappola, Thomas P., Lemieux, Madeleine, Plutzky, Jorge, Bradner, James E., Haldar, Saptarsi M.·2013·Cell

DOI 10.1016/j.cell.2013.07.013PMC PMC4090947

Open this paper in CoChat — free account Open PDF

Abstract

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.

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.2013.07.013

Cites

63 of 63 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.

1 retracted

RETRACTED: Segregation of atrial-specific and inducible expression of an atrial natriuretic factor transgene in an in vivo murine model of cardiac hypertrophy.
Rockman, H. A., Ross, R. S., Harris, A. N., Knowlton, K. U., Steinhelper, M. E., Field, L. J., Ross, J., & Chien, K. R. (1991) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.88.18.8277 · Cited by 807 · cited 1×
“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).”
Retracted
Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles
Subramanian, 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×
“Using gene set enrichment analysis (GSEA) (Subramanian et al., 2005), we compared our set of TAC-induc-”
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
Prognostic implications of echocardiographically determined left ventricular mass in the Framingham Heart study
Levy, D., Garrison, R. J., Savage, D. D., Kannel, W. B., & Castelli, W. P. (1990) · New England Journal of Medicine · doi:10.1056/nejm199005313222203 · Cited by 5,699 · cited 1×
“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-citation
Selective Inhibition of Tumor Oncogenes by Disruption of Super-Enhancers
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. (2013) · Cell · doi:10.1016/j.cell.2013.03.036 · Cited by 2,961 · cited 3×
“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-citation
BET 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).”
InfluentialSelf-citation
Systematic discovery of regulatory motifs in human promoters and 3′ UTRs by comparison of several mammals
Xie, X., Lu, J., Kulbokas, E. J., Golub, T. R., Mootha, V., Lindblad-Toh, K., Lander, E. S., & Kellis, M. (2005) · Nature · doi:10.1038/nature03441 · Cited by 1,872 · cited 1×
“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).”
Self-citation

Flagged first, then by citations

Show all 63 references

Sorted by citations

Items 201–300 of 417

Functional coordination of BET family proteins underlies altered transcription associated with memory impairment in fragile X syndrome
Kim, S.-K., Liu, X., Park, J., Um, D., Kilaru, G., Chiang, C., Kang, M., Huber, K. M., Kang, K., & Kim, T.-K. (2021) · Science Advances · doi:10.1126/sciadv.abf7346 · Cited by 23
“Pharmacologic inhibition of BET protein function has been a promising therapeutic strategy for several diseases including cancers (4, 12–16), inflammation (17), and heart failure (18).”
Background
Differential Activation of P-TEFb Complexes in the Development of Cardiomyocyte Hypertrophy following Activation of Distinct G Protein-Coupled Receptors
Martin, R., Sun, Y., MacKinnon, S., Cuccia, L., Pagé, V., Hébert, T. E., & Tanny, J. C. (2020) · Molecular and Cellular Biology · doi:10.1128/mcb.00048-20 · Cited by 22
“15 cardiac tissue not enriched for cardiomyocytes or in vitro cardiomyocyte studies which reported 321 conflicting evidence regarding changes in Brd4 expression (18, 21).”
BackgroundInfluential
Rational design of 5-((1H-imidazol-1-yl)methyl)quinolin-8-ol derivatives as novel bromodomain-containing protein 4 inhibitors
Xing, J., Zhang, R., Jiang, X., Hu, T., Wang, X., Qiao, G., Wang, J., Yang, F., Luo, X., Chen, K., et al. (2018) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2018.11.018 · Cited by 23
Self-citation
4-Acyl Pyrroles as Dual BET-BRD7/9 Bromodomain Inhibitors Address BETi Insensitive Human Cancer Cell Lines
Hügle, M. J., Regenass, P., Warstat, R., Hau, M., Schmidtkunz, K., Lucas, X., Wohlwend, D., Einsle, O., Jung, M., Breit, B., et al. (2020) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.0c00478 · Cited by 23
BRD4 Inhibition Protects Against Myocardial Ischemia/Reperfusion Injury by Suppressing Inflammation and Oxidative Stress Through the PI3K/AKT Signaling Pathway
Wei, H., Xue, Q., Sun, L., & Lv, J. (2021) · Journal of Cardiovascular Pharmacology · doi:10.1097/fjc.0000000000001138 · Cited by 21
Disruption of cardiac Med1 inhibits RNA polymerase II promoter occupancy and promotes chromatin remodeling
Hall, D. D., Spitler, K. M., & Grueter, C. E. (2018) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00580.2018 · Cited by 21
Bromodomains: pockets with therapeutic potential
Papavassiliou, K. A., & Papavassiliou, A. G. (2014) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2014.06.004 · Cited by 20
Genomic Binding Patterns of Forkhead Box Protein O1 Reveal Its Unique Role in Cardiac Hypertrophy
Pfleger, J. M., Coleman, R. C., Ibetti, J., Roy, R., Kyriazis, I. D., Gao, E., Drosatos, K., & Koch, W. J. (2020) · Circulation · doi:10.1161/circulationaha.120.046356 · Cited by 20
Interleukin-33 induces angiogenesis after myocardial infarction via AKT/eNOS signaling pathway
Yu, J., Li, Y., Hu, J., & Wang, Y. (2024) · International Immunopharmacology · doi:10.1016/j.intimp.2024.113433 · Cited by 19
Genome-Wide Dynamics of Nascent Noncoding RNA Transcription in Porcine Heart After Myocardial Infarction
Kaikkonen, M. U., Halonen, P. J., Liu, O. H.-F., Turunen, T. A., Pajula, J. J., Moreau, P. R., Selvarajan, I., Tuomainen, T., Aavik, E., Tavi, P., et al. (2017) · Circulation Cardiovascular Genetics · doi:10.1161/circgenetics.117.001702 · Cited by 19
Design, synthesis and biological evaluation of purine-based derivatives as novel JAK2/BRD4(BD2) dual target inhibitors
Guo, Y. C., Zou, Y., Chen, Y. X., Deng, D., Zhang, Z., Liu, K., Tang, M., Yang, T., Fu, S., Zhang, C., et al. (2023) · Bioorganic Chemistry · doi:10.1016/j.bioorg.2023.106386 · Cited by 19
High-sensitive nascent transcript sequencing reveals BRD4-specific control of widespread enhancer and target gene transcription
Bressin, A., Jasnovidova, O., Arnold, M., Altendorfer, E., Trajkovski, F., Kratz, T. A., Handzlik, J. E., Hnisz, D., & Mayer, A. (2023) · Nature Communications · doi:10.1038/s41467-023-40633-y · Cited by 22
Epigenetic Regulation of Fibroblasts and Crosstalk between Cardiomyocytes and Non-Myocyte Cells in Cardiac Fibrosis
Chu, L., Xie, D., & Xu, D. (2023) · Biomolecules · doi:10.3390/biom13091382 · Cited by 19
“In the mouse models of TAC and Plnr9c mutationinduced dilated cardiomyopathy (DCM), JQ1 has demonstrated the ability to improve cardiac contractile dysfunction, reduce cardiomyocyte hypertrophy, and attenuate cardiac fibrosis [101].”
Background
Erythropoiesis provides a BRD's eye view of BET protein function
Stonestrom, A. J., Hsu, S. C., Werner, M. T., & Blobel, G. A. (2016) · Drug Discovery Today Technologies · doi:10.1016/j.ddtec.2016.05.004 · Cited by 21
“Preclinical studies have also demonstrated the potential efficacy of BET inhibition in applications that would require chronic administration such as heart failure, and type I diabetes mellitus [67,68].”
Background
Receptor- and cellular compartment-specific activation of the cAMP/PKA pathway by α1-adrenergic and ETA endothelin receptors
Martin, R., Sun, Y., Bourque, K., Audet, N., Inoue, A., Tanny, J. C., & Hébert, T. E. (2018) · Cellular Signalling · doi:10.1016/j.cellsig.2018.01.002 · Cited by 19
Overexpression of Ubiquitin-Specific Protease 2 (USP2) in the Heart Suppressed Pressure Overload-Induced Cardiac Remodeling
Xing, J., Li, P., Hong, J., Wang, M., Liu, Y., Gao, Y., Dong, J., Gu, H., & Li, L. (2020) · Mediators of Inflammation · doi:10.1155/2020/4121750 · Cited by 19
SPOP-mediated degradation of BRD4 dictates cellular sensitivity to BET inhibitors
Dai, X., Wang, Z. P., & Wei, W. (2017) · Cell Cycle · doi:10.1080/15384101.2017.1388973 · Cited by 20
“Mechanistically, histone acetyltransferases (HATs) can add acetyl groups to histone Lys residues as writers, while histone deacetylases (HDACs) and Sirtuins (SIRTs) can remove acetyl groups as erasers.(2) On the other hand, Bromodomain (BRD) proteins bind to acetylated lysine (Kac) and function as readers of lysine ac…”
Background
BET-Family Bromodomains Can Recognize Diacetylated Sequences from Transcription Factors Using a Conserved Mechanism
Patel, K., Solomon, P. D., Walshe, J. L., Ford, D., Wilkinson‐White, L. E., Payne, R. J., Low, J. K. K., & Mackay, J. P. (2021) · Biochemistry · doi:10.1021/acs.biochem.0c00816 · Cited by 19
Targeting transcription in heart failure via CDK7/12/13 inhibition
Hsu, A., Duan, Q., Day, D. S., Luo, X., McMahon, S., Huang, Y., Feldman, Z. B., Jiang, Z., Zhang, T., Liang, Y., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-31541-8 · Cited by 17
Self-citation
BET Proteins: An Approach to Future Therapies in Transplantation
Suárez-Álvarez, B., Rodríguez, R. M. A., Ruiz‐Ortega, M., & López‐Larrea, C. (2017) · American Journal of Transplantation · doi:10.1111/ajt.14221 · Cited by 17
Bromodomain and Extraterminal (BET) Proteins Regulate Hepatocyte Proliferation in Hepatocyte-Driven Liver Regeneration
Russell, J. O., Ko, S., Saggi, H., Singh, S., Poddar, M., Shin, D., & Monga, S. P. (2018) · American Journal Of Pathology · doi:10.1016/j.ajpath.2018.02.006 · Cited by 18
Inhibition of BET bromodomain attenuates angiotensin II induced abdominal aortic aneurysm in ApoE−/− mice
Duan, Q., Mao, X., Liao, C., Zhou, H., Sun, Z., Deng, X., Hu, Q., Qi, J., Zhang, G., Huang, H., et al. (2016) · International Journal of Cardiology · doi:10.1016/j.ijcard.2016.08.238 · Cited by 17
Self-citation
BET bromodomain is a novel regulator of TAZ and its activity
Duan, Q., Xiao, Y., Zhu, L., Liu, Z., Mao, X., Zhou, Z., Liao, C., Cai, J., Huang, F., Liu, Z., et al. (2016) · Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms · doi:10.1016/j.bbagrm.2016.10.001 · Cited by 17
Self-citation
Bromodomain and Extra Terminal Protein Inhibitors Promote Pancreatic Endocrine Cell Fate
Huijbregts, L., Petersen, M. B. K., Berthault, C., Hansson, M. D., Aïello, V., Rachdi, L., Grapin‐Botton, A., Honoré, C., & Scharfmann, R. (2019) · Diabetes · doi:10.2337/db18-0224 · Cited by 17
“Brd4 has been the most studied BET member because it was shown to modulate RNA polymerase II activity either by interacting with members of the transcription initiation complex, such as pTEFb and mediator (44–46), or by directly releasing proximally paused RNA polymerase II (47).”
Background
Bromodomain‐containing protein 4 and its role in cardiovascular diseases
Li, L., Xie, W., Gui, Y., & Zheng, X. (2020) · Journal of Cellular Physiology · doi:10.1002/jcp.30225 · Cited by 17
“A study by Anand et al. (2013) revealed that BRD4 has the highest expression of the BET genes in isolated adult hypertrophic cardio- myocytes and hypertrophic cardiac tissue.”
Background
Using Omics to Identify Novel Therapeutic Targets in Heart Failure
Lteif, C., Huang, Y., Guerra, L. A., Gawronski, B. E., & Duarte, J. D. (2024) · Circulation Genomic and Precision Medicine · doi:10.1161/circgen.123.004398 · Cited by 20
“…acetyl-lysine reader proteins appears to reduce cardiomyocyte hypertrophy in vitro and both LV hypertrophy and fibrosis in mouse models of HF. 41,42 In addition, the BET inhibitor apabetalone decreased first-hospitalizations for HF, total HF hospitalizations, and the composite of cardiovascular…”
Background
Time and Technology Will Tell
Reed, B. N., Street, S. E., & Jensen, B. C. (2014) · Heart Failure Clinics · doi:10.1016/j.hfc.2014.07.002 · Cited by 17
Toward a New Paradigm for Targeted Natriuretic Peptide Enhancement in Heart Failure
Gidlöf, O. (2021) · Frontiers in Physiology · doi:10.3389/fphys.2021.650124 · Cited by 18
Bromodomain Inhibitor JQ1 Provides Novel Insights and Perspectives in Rhabdomyosarcoma Treatment
Marchesi, I., Fais, M., Fiorentino, F., Bordoni, V., Sanna, L., Zoroddu, S., & Bagella, L. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23073581 · Cited by 14
“BRD4, one of the most studied member of the BET-containing protein family, is an epigenetic factor that is associated with active promoters and enhancers of transcriptionally active genes [18,34].”
Background
Epigenetics
Jain, R., & Epstein, J. A. (2024) · Advances in experimental medicine and biology · doi:10.1007/978-3-031-44087-8_18 · Cited by 16
Identification of Candidate Long Noncoding RNAs Associated with Left Ventricular Hypertrophy
Zhang, L., Hamad, E. A., Vausort, M., Funakoshi, H., Feldman, A. M., Wagner, D. R., & Devaux, Y. (2014) · Clinical and Translational Science · doi:10.1111/cts.12234 · Cited by 15
In vitro assessment of anti-fibrotic drug activity does not predict in vivo efficacy in murine models of Duchenne muscular dystrophy
Théret, M., Low, M., Rempel, L., Li, F. F., Tung, L. W., Contreras, O., Chang, C.-K., Wu, A., Soliman, H. S., & Rossi, F. M. V. (2021) · Life Sciences · doi:10.1016/j.lfs.2021.119482 · Cited by 22
Relevance of BET Family Proteins in SARS-CoV-2 Infection
Lara-Ureña, N., & García‐Domínguez, M. (2021) · Biomolecules · doi:10.3390/biom11081126 · Cited by 15
“In heart failure models, BRD4 occupies the majority of activated enhancers and BET inhibition disturbs associated transcription, suppressing cardiomyocyte hypertrophy [234].”
Background
Epitranscriptional regulation of cardiovascular development and disease
Dorn, G. W., & Matkovich, S. J. (2014) · The Journal of Physiology · doi:10.1113/jphysiol.2014.283234 · Cited by 15
“…‘erase’ acetylation and methylation marks on histones and indirectly affect DNA structure, BET bromodomain proteins represent an important family of histone mark ‘readers’ that directly interact with acetylated lysines and activate pathological gene transcription in the heart (Anand et al. 2013).”
Background
BET Protein-Mediated Transcriptional Regulation in Heart Failure
Ijaz, T., & Burke, M. A. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22116059 · Cited by 15
Cytoprotective, Cytotoxic and Cytostatic Roles of Autophagy in Response to BET Inhibitors
Elshazly, A. M., & Gewirtz, D. A. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241612669 · Cited by 14
“[30,31], inflammatory disease [32] and cancer [33,34].”
Background
The Year in Cardiology 2013: heart failure
Ertl, G., & Ruschitzka, F. T. (2014) · European Heart Journal · doi:10.1093/eurheartj/eht555 · Cited by 14
Chromatin Remodeling Drives Immune-Fibroblast Crosstalk in Heart Failure PathogenesisPreprint
Alexanian, M., Padmanabhan, A., Nishino, T., Travers, J. G., Ye, L., Lee, C. Y., Sadagopan, N., Huang, Y., Pelonero, A., Auclair, K., et al. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.01.06.522937 · Cited by 14
Self-citation
Molecular Interplay of Gene Network Dynamics, Epigenetic Regulation, and Therapeutic Mapping in Cardiovascular Disease
Akanda, M. R., Sabuj, M. S. S., Salam, S. M. A., & Jahan, E. (2025) · Cardiovascular Drugs and Therapy · doi:10.1007/s10557-025-07739-5 · Cited by 14
(+)-JQ-1 alleviates cardiac injury in myocardial infarction by inhibiting ferroptosis through the NAMPT/SIRT1 pathway
Yang, M., Wang, T., Shao, J., Ran, X., Xiao, R., Zhao, R., Wu, C., Ji, M., Tian, W., Sun, H., et al. (2025) · Cell Death and Disease · doi:10.1038/s41419-025-07880-x · Cited by 15
“JQ-1 administration suppresses phenylephrine-induced cellular hypertrophy in NRVMs and inhibits transverse aortic constriction-induced pathological cardiac hypertrophy and heart failure in mice [17].”
Molecular basis of GDF15 induction and suppression by drugs in cardiomyocytes and cancer cells toward precision medicine
Winter, L.-M., Reinhardt, D., Schatter, A., Tissen, V., Wiora, H., Gerlach, D., Tontsch-Grunt, U., Colbatzky, F., Stierstorfer, B., & Yun, S. (2023) · Scientific Reports · doi:10.1038/s41598-023-38450-w · Cited by 15
BRD4 inhibition rewires cardiac macrophages toward a protective phenotype marked by low MHC class II expression
Schuetze, K. B., Stratton, M. S., Bagchi, R. A., Hobby, A. R. H., Felisbino, M. B., Rubino, M., Toni, L. S., Reges, C. R., Cavasin, M. A., McMahan, R. H., et al. (2024) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00438.2024 · Cited by 14
Super-enhancers in tumors: unraveling recent advances in their role in Oncogenesis and the emergence of targeted therapies
Ji, Y., Li, B., Lin, R., Yuan, J. T., Han, Y., Du, Y., & Zhao, Y. (2025) · Journal of Translational Medicine · doi:10.1186/s12967-025-06098-x · Cited by 14
Emerging Epigenetic Therapies for the Treatment of Cardiac Fibrosis
Garitano, N., Aguado‐Alvaro, L. P., & Pelacho, B. (2025) · Biomedicines · doi:10.3390/biomedicines13051170 · Cited by 13
“Finally, the BRD4 inhibitor JQ1 has shown potential in reducing cardiac fibrosis by suppressing key fibrotic markers and fibroblast contractility [110,111].”
The Killing of Human Neuroblastoma Cells by the Small Molecule JQ1 Occurs in a p53-Dependent Manner
Mazar, J., Gordon, C., Naga, V., & Westmoreland, T. J. (2020) · Anti-Cancer Agents in Medicinal Chemistry · doi:10.2174/1871520620666200424123834 · Cited by 13
BMAL1 regulates transcription initiation and activates circadian clock gene expression in mammals
Xiong, W., Li, J., Zhang, E. E., & Huang, H. (2016) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2016.04.009 · Cited by 15
Spotlight on epigenetic reprogramming in cardiac regeneration
Soler‐Botija, C., Forcales, S. V., & Bayés‐Genís, A. (2019) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2019.04.009 · Cited by 13
Targeting bromodomain-containing proteins to prevent spontaneous preterm birth
Lim, R., Nguyen‐Ngo, C., & Lappas, M. (2019) · Clinical Science · doi:10.1042/cs20190919 · Cited by 13
Recent discoveries of the role of histone modifications and related inhibitors in pathological cardiac hypertrophy
Wu, K., Chen, Q., Leung, C., Sun, N., Gao, F., & Chen, Z. (2024) · Drug Discovery Today · doi:10.1016/j.drudis.2024.103878 · Cited by 14
Epigenetic therapies - a new direction in clinical medicine
Stein, R. A. (2014) · International Journal of Clinical Practice · doi:10.1111/ijcp.12436 · Cited by 12
Histone Deacetylase 6 Inhibitor JS28 Prevents Pathological Gene Expression in Cardiac Myocytes
Ngo, V., Fleischmann, B. K., Jung, M., Hein, L., & Lother, A. (2022) · Journal of the American Heart Association · doi:10.1161/jaha.122.025857 · Cited by 12
It’s Time for An Epigenomics Roadmap of Heart Failure
Papait, R., Corrado, N., Rusconi, F., Serio, S., & Latronico, M. V. G. (2015) · Current Genomics · doi:10.2174/1389202916666150505183624 · Cited by 13
Promoter-proximal regulation of gene transcription: Key factors involved and emerging role of general transcription factors in assisting productive elongation
Pal, S., & Biswas, D. (2023) · Gene · doi:10.1016/j.gene.2023.147571 · Cited by 11
BRD4 as a therapeutic target for atrial fibrosis and atrial fibrillation
Song, S., Yuan, J., Fang, G., Li, Y., Ding, S., Wang, Y., & Wang, Q. (2024) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2024.176714 · Cited by 12
Nuclear m6A modification regulates satellite transcription and chromosome segregation
Huang, C., Shu, X., Zhou, S., Mi, Y., Bian, H., Li, T., Li, T., Ying, X., Cheng, C., Liu, D., et al. (2025) · Nature Chemical Biology · doi:10.1038/s41589-025-01900-9 · Cited by 13
“EP300/ CREB binding protein complex is known to catalyze the formation of H3K27ac 54 , and BRD4 commonly acts as an epigenetic reader to recognize H3K27ac and promotes subsequent gene transcription by RNA Pol II 55,56 .”
Transcriptome Analysis of Hypertrophic Heart Tissues from Murine Transverse Aortic Constriction and Human Aortic Stenosis Reveals Key Genes and Transcription Factors Involved in Cardiac Remodeling Induced by Mechanical Stress
Yu, P., Zhang, B., Liu, M., Yu, Y., Zhao, J., Zhang, C., Li, Y., Zhang, L., Yang, X., Jiang, H., et al. (2019) · Disease Markers · doi:10.1155/2019/5058313 · Cited by 11
Selection of reference genes for normalization of quantitative polymerase chain reaction data in mouse models of heart failure
Li, Q., HU, T., Chen, L., Sun, J., Xie, J., LI, R., & Xu, B. (2014) · Molecular Medicine Reports · doi:10.3892/mmr.2014.2750 · Cited by 11
Four Dimensions of the Cardiac Myocyte Epigenome: from Fetal to Adult Heart
Rommel, C., & Hein, L. (2020) · Current Cardiology Reports · doi:10.1007/s11886-020-01280-7 · Cited by 11
Apabetalone – Bet Protein Inhibition in Cardiovascular Disease and Type 2 Diabetes
Brandts, J., & Ray, K. K. (2020) · Future Cardiology · doi:10.2217/fca-2020-0017 · Cited by 11
Dioxin Disrupts Dynamic DNA Methylation Patterns in Genes That Govern Cardiomyocyte Maturation
de Gannes, M., Ko, C., Zhang, X., Biesiada, J., Niu, L., Koch, S. E., Medvedovic, M., Rubinstein, J., & Puga, A. (2020) · Toxicological Sciences · doi:10.1093/toxsci/kfaa153 · Cited by 11
Bromodomain Inhibition Reveals FGF15/19 As a Target of Epigenetic Regulation and Metabolic Control
Kozuka, C., Efthymiou, V., Sales, V., Zhou, L., Osataphan, S. A., Yuchi, Y., CHIMENE-WEISS, J. I., Mulla, C. M., ISGANAITIS, E. M., Desmond, J., et al. (2022) · Diabetes · doi:10.2337/db21-0574 · Cited by 11
Self-citation
Correlation of Bromodomain Protein BRD4 Expression With Epithelial–Mesenchymal Transition and Disease Severity in Chronic Rhinosinusitis With Nasal Polyps
Zhou, X., Cui, Z., Liu, Y., Yue, Z., Xie, F., Ding, L., Xu, S., Han, J., & Zhang, H. (2020) · Frontiers in Medicine · doi:10.3389/fmed.2020.00413 · Cited by 11
“Bromodomain-containing protein 4 has been found in many other types of cells (31, 32) but has never been reported in the nasal tissues.”
Background
The roles and mechanisms of epigenetic regulation in pathological myocardial remodeling
Zhao, K., Mao, Y., Li, Y., Yang, C., Wang, K., & Zhang, J. (2022) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2022.952949 · Cited by 10
Spinal-Specific Super Enhancer in Neuropathic Pain
Tao, Y., Wang, Q., Li, X., Liu, Y., Sun, R.-H., Xu, H., Zhang, M., Siyuan, L., Li, Y., Wang, H., et al. (2023) · Journal of Neuroscience · doi:10.1523/jneurosci.1006-23.2023 · Cited by 10
Cardiac Remodeling and Ventricular Pacing: From Genes to Mechanics
Malikides, O., Simantirakis, E., Zacharis, E. A., Fragkiadakis, K., KOCHIADAKIS, G. E., & Marketou, M. E. (2024) · Genes · doi:10.3390/genes15060671 · Cited by 13
“Increasing evidence has indicated that gene expression, leading to cardiac remodeling, is mediated by transcription factors and the epigenetics process [14,15,16] and occurs as a result of dysregulation in genes encoding a variety of proteins, including sarcomeric and structural proteins.”
Background
Environmental factors influence somatic cell reprogramming to cardiomyocyte-like cells
Handel, B. V., Wang, L., & Ardehali, R. (2021) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2021.05.028 · Cited by 10
Transcriptional regulation of cardiac fibroblast phenotypic plasticity
Villar, K. N. B., Liu, X., & Small, E. M. (2022) · Current Opinion in Physiology · doi:10.1016/j.cophys.2022.100556 · Cited by 11
TAF1 bromodomain inhibition as a candidate epigenetic driver of congenital heart disease
Leigh, R. S., Välimäki, M. J., Kaynak, B. L., & Ruskoaho, H. J. (2023) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2023.166689 · Cited by 10
Targeting transcriptional machinery to inhibit enhancer-driven gene expression in heart failure
Minerath, R. A., Hall, D. D., & Grueter, C. E. (2019) · Heart Failure Reviews · doi:10.1007/s10741-019-09792-3 · Cited by 12
Synthesis and elaboration of N-methylpyrrolidone as an acetamide fragment substitute in bromodomain inhibition
Hilton-Proctor, J. P., Ilyichova, O. V., Zheng, Z., Jennings, I. G., Johnstone, R. W., Shortt, J., Mountford, S. J., Scanlon, M. J., & Thompson, P. E. (2019) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2019.115157 · Cited by 10
Cardiac-specific overexpression of PRMT5 exacerbates pressure overload-induced hypertrophy and heart failure
Katanasaka, Y., Sunagawa, Y., Sakurai, R., Tojima, M., Naruta, R., Hojo, Y., Kawase, Y., Hamabe‐Horiike, T., Mori, K., Hasegawa, K., et al. (2025) · Journal of Biomedical Science · doi:10.1186/s12929-025-01162-6 · Cited by 9
Measuring hypertrophy in neonatal rat primary cardiomyocytes and human iPSC-derived cardiomyocytes
Bourque, K., Hawey, C., Jones-Tabah, J., Pétrin, D., Martin, R., Sun, Y., & Hébert, T. E. (2021) · Methods · doi:10.1016/j.ymeth.2021.12.006 · Cited by 12
Epigenetic Reader Bromodomain Containing Protein 2 Facilitates Pathological Cardiac Hypertrophy via Regulating the Expression of Citrate Cycle Genes
Lin, Z., Li, Z., Guo, Z., Cao, Y., Li, J., Liu, P., & Li, Z. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.887991 · Cited by 9
State of change: epigenetic and mitochondrial regulation of cardiac fibroblast activation
Garvin, A. M., & Hale, T. M. (2022) · Current Opinion in Physiology · doi:10.1016/j.cophys.2022.100557 · Cited by 9
Selective BD2 Inhibitor Exerts Anti-Fibrotic Effects via BRD4/FoxM1/Plk1 Axis in Orbital Fibroblasts From Patients With Thyroid Eye Disease
Xie, Y., Pan, Y., Chen, Q., Chen, Y., Chen, G., Wang, M., Zeng, P. C., Li, Z., Li, Z., Wang, S., et al. (2023) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.64.7.9 · Cited by 9
Potential Applications of Induced Pluripotent Stem Cells for Cardiovascular Diseases
Wang, X., Han, Z., Yu, Y., Xu, Z., Cai, B., & Yuan, Y. (2018) · Current Drug Targets · doi:10.2174/1389450120666181211164147 · Cited by 9
Crystal Structure of the first bromodomain of human BRD4 in complex with 5-((4-fluoro-1H-imidazol-1-yl)methyl)quinolin-8-ol
Xing, J., Zhang, R., Zheng, M. Y., Luo, C., & Jiang, X. R. (2018) · Worldwide Protein Data Bank · doi:10.2210/pdb6afr/pdb · Cited by 9
Self-citation
Orally Bioavailable BRD4 BD1 Inhibitor ZL0516 Effectively Suppresses Colonic Inflammation in Animal Models of Inflammatory Bowel Disease
Ma, Z., McAninch, S. B., Liu, Z., Zhang, C., Chen, H., He, J., Yang, W., Panganiban, R. P., Cong, Y., Yochum, G. S., et al. (2025) · ACS Pharmacology & Translational Science · doi:10.1021/acsptsci.5c00068 · Cited by 8
Roles of Brd4 in Vascular Smooth Muscle Cells: Implications for Aging and Vascular Dysfunction
Sun, J., Gui, Y., Yin, H. R., Yan, B., Chen, Y.-X., Belke, D. D., Hill, J. A., Zhou, S., & Zheng, X. (2025) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.124.322158 · Cited by 9
Inflammation-resolution signalling in cardiac repair, remodelling, and heart failure
Halade, G. V., Bäck, M., & Kain, V. (2025) · European Heart Journal Open · doi:10.1093/ehjopen/oeaf157 · Cited by 9
How to mend a broken heart: adult and induced pluripotent stem cell therapy for heart repair and regeneration
Wegener, M., Bader, A., & Giri, S. (2015) · Drug Discovery Today · doi:10.1016/j.drudis.2015.02.010 · Cited by 8
Gβγ subunits colocalize with RNA polymerase II and regulate transcription in cardiac fibroblasts
Khan, S. M., Martin, R., Bayne, A. N., Pétrin, D., Bourque, K., Jones-Tabah, J., Bouazza, C. A., Blaney, J., Lau, J., Martins-Cannavino, K., et al. (2023) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2023.103064 · Cited by 8
Elucidating the mechanisms of transcription regulation during heart development by next-generation sequencing
Nimura, K., & Kaneda, Y. (2015) · Journal of Human Genetics · doi:10.1038/jhg.2015.84 · Cited by 7
Drugging transcription in heart failure
Padmanabhan, A., & Haldar, S. M. (2019) · The Journal of Physiology · doi:10.1113/jp276745 · Cited by 8
“…cardiac tissue from this study revealed that BET inhibition suppressed the activation of specific cardiac gene expression programmes that enrich for targets of nuclear factor of activated T cells (NFAT), nuclear factor-κB (NFκB) and GATA binding protein 4 (GATA4) signalling (Anand et al. 2013).”
BackgroundMethodResultInfluentialSelf-citation
Engineering “Antimicrobial Peptides” and Other Peptides to Modulate Protein-Protein Interactions in Cancer
Rubin, S. J. S., & Qvit, N. (2020) · Current Topics in Medicinal Chemistry · doi:10.2174/1568026620666201021141401 · Cited by 8
Exploring the Role of Genetic and Genomic Factors in Therapeutic Response to Heart Failure: A Comprehensive Analytical Review
Ferro, A., Segreti, A., Crispino, S. P., Cricco, R., Cristo, A. D., Ciancio, M., Gurrieri, F., Ussia, G. P., & Grigioni, F. (2025) · Genes · doi:10.3390/genes16070801 · Cited by 8
“Additionally, BET inhibitors such as JQ1 are being explored as promising treatments for HF [46].”
Effect of BRD4 Inhibitor on Cognitive Deficit and c-Fos /BDNF level in rats with Alzheimer's disease
Faraji, N., Badrikoohi, M., & Babaei, P. (2023) · Neuroscience and Behavioral Physiology · doi:10.1007/s11055-023-01342-7 · Cited by 7
“Furthermore, distinct alteration in the proteins level of c-Fos/BDNF after BRD4 inhibition in the various physiological and pathophysiological situations indicate that transcriptional effects of BET inhibitors are not only highly specific to the organism status being examined [8], and characteristic of treatment (acut…”
Background
Research Progress of Selective Small Molecule Bromodomain-Containing Protein 9 Inhibitors
Ma, H., Zhang, J., Zheng, P., Zhenwei, W., & Huibin, Z. (2018) · Future Medicinal Chemistry · doi:10.4155/fmc-2017-0243 · Cited by 7
Enabling cancer target validation with genetically encoded systems for ligand-induced protein degradation
Zhang, Y., & Erb, M. A. (2021) · Current Research in Chemical Biology · doi:10.1016/j.crchbi.2021.100011 · Cited by 7
Histone Modifications in Cardiovascular Disease: Mechanisms and Therapeutic Opportunities
Zheng, Y., Gao, Y., Guo, M., Wang, L., Zheng, X., Liao, Y., Li, Y., Zhu, J.-P., & Wei, J. (2026) · MedComm · doi:10.1002/mco2.70765 · Cited by 7
Understanding Immune Responses to Surgical Transplant Procedures in Stevens Johnsons Syndrome Patients
Soifer, M., Mousa, H. M., Levy, R. B., & Perez, V. L. (2021) · Frontiers in Medicine · doi:10.3389/fmed.2021.656998 · Cited by 6
Transcriptional plasticity of fibroblasts in heart disease
Micheletti, R., & Alexanian, M. (2022) · Biochemical Society Transactions · doi:10.1042/bst20210864 · Cited by 7
Regulation of Cell Plasticity by Bromodomain and Extraterminal Domain (BET) Proteins: A New Perspective in Glioblastoma Therapy
Gargano, D., Segatto, M., & Bartolomeo, S. D. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24065665 · Cited by 9
Identification of transcription factors MYC and C/EBPβ mediated regulatory networks in heart failure based on gene expression omnibus datasets
Wang, H., Wang, X., Xu, L., & Cao, H. (2020) · BMC Cardiovascular Disorders · doi:10.1186/s12872-020-01527-9 · Cited by 7
P-TEFb et Brd4
Furlan, A., Agbazahou, F., Henry, M., Pisfil, M. G., Nézet, C. L., Champelovier, D., Fournier, M., Vandenbunder, B., Bidaux, G., & Héliot, L. (2018) · médecine/sciences · doi:10.1051/medsci/20183408015 · Cited by 6
Unraveling the Role of Bromodomain and Extra-Terminal Proteins in Human Uterine Leiomyosarcoma
Yang, Q., Falahati, A., Khosh, A., Lastra, R. R., Boyer, T., & Al-Hendy, A. A. (2024) · Cells · doi:10.3390/cells13171443 · Cited by 6
“In addition, BET inhibitors also provide multiple beneficial effects on anti-inflammation [47], heart failure [62], spermatogenesis [63], and chemoresistance [64,65].”
Background
Targeting Viperin prevents coxsackievirus B3-induced acute heart failure
Yuan, Y., Qian, L., Miao, Y., Cui, Q., Cao, T., Yu, Y., Zhang, T., Zhao, Q., Zhang, R., Ren, T., et al. (2025) · Cell Discovery · doi:10.1038/s41421-025-00778-0 · Cited by 5
“SERCA2a, BET bromodomain protein, and mitochondrial DNA regulate transverse aortic constriction (TAC)-induced HF 11 – 13 .”
Self-citation
Transcriptional signature of cardiac myocyte recovery in mice and human reveals persistent upregulation of epigenetic factors
Roth, R., Häckh, M., Schnick, T., Rommel, C., Koentges, C., Bugger, H., Domisch, C., Bristow, M. R., Ambardekar, A. V., McKinsey, T. A., et al. (2025) · Epigenetics · doi:10.1080/15592294.2025.2506625 · Cited by 5
“For the heart, in particular the role of the bromodomain protein BRD4 has been well studied [29–32].”
Roles of Bromodomain Extra Terminal Proteins in Metabolic Signaling and Diseases
Wu, D., & Duan, Q. (2022) · Pharmaceuticals · doi:10.3390/ph15081032 · Cited by 5
“found that BETs function as pause-release factors critical to the expression of pathological hypertrophic genes, and that inhibition of these BETs suppresses cardiomyocyte hypertrophy in vitro and pathological cardiac remodeling in vivo [30].”
Background
The Bromodomain as the Acetyl-Lysine Binding Domain in Gene Transcription
Smith, S. G., & Zhou, M. (2015) · Springer eBooks · doi:10.1007/978-3-319-18102-8_1 · Cited by 4
“2013), and the BET family has recently been shown to play a role in the pathogenesis of heart failure (Anand et al. 2013).”
Background

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: Brown, Jonathan D.
Lin, Charles Y.
Qi, Jun
Zhang, Rongli
Alaiti, M. Amer
Alazem, Kareem
Margulies, Kenneth B.
Cappola, Thomas P.
Lemieux, Madeleine
Plutzky, Jorge
Bradner, James E.
Haldar, Saptarsi M.
Venue: Cell
Publisher: Elsevier BV
Published: 2013-08
Volume: 154
Issue: 3
Pages: 569-582
ISSN: 0092-8674 (ISSN-L)
DOI: 10.1016/j.cell.2013.07.013
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: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 365 d)
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

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

BET Bromodomains Mediate Transcriptional Pause Release in Heart Failure

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