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 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.
Overview
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
Cites
Statistics
Verification
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?
The cited source says what the claim attributes to it.
In the citing paper
“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]
The cited source says what the claim attributes to it.
In the citing paper
“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]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
1 retracted
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).”
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×
“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
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-citationSelective 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-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).”
InfluentialSelf-citationXie, 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
Cited by
Sorted by citations
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-citation
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
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
