The DOI matches its Crossref record; 45 of the 45 references it cites were found in a registry or an index.
HDAC7 regulates histone 3 lysine 27 acetylation and transcriptional activity at super-enhancer-associated genes in breast cancer stem cells
Open accessAbstract
Chromatin regulation through histone modifications plays an essential role in coordinated expression of multiple genes. Alterations in chromatin induced by histone modifiers and readers regulate critical transcriptional programs involved in both normal development and tumor differentiation. Recently, we identified that histone deacetylases HDAC1 and HDAC7 are necessary to maintain cancer stem cells (CSCs) in both breast and ovarian tumors. Here, we sought to investigate the CSC-specific function of HDAC1 and HDAC7 mechanistically by using a stem-like breast cancer (BrCa) cell model BPLER and matched nonstem tumor cell (nsTC)-like HMLER, along with conventional BrCa cell lines with different CSC enrichment levels. We found that HDAC1 and HDAC3 inhibition or knockdown results in HDAC7 downregulation, which is associated with a decrease in histone 3 lysine 27 acetylation (H3K27ac) at transcription start sites (TSS) and super-enhancers (SEs) prominently in stem-like BrCa cells. Importantly, these changes in chromatin landscape also correlate with the repression of many SE-associated oncogenes, including c-MYC, CD44, CDKN1B, SLUG, VDR, SMAD3, VEGFA, and XBP1. In stem-like BrCa cells, HDAC7 binds near TSS and to SEs of these oncogenes where it appears to contribute to both H3K27ac and transcriptional regulation. These results suggest that HDAC7 inactivation, directly or through inhibition of HDAC1 and HDAC3, can result in the inhibition of the CSC phenotype by downregulating multiple SE-associated oncogenes. The CSC selective nature of this mechanism and the prospect of inhibiting multiple oncogenes simultaneously makes development of HDAC7 specific inhibitors a compelling objective.
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?
In the citing paper
“HDAC7 controls the deposition of H3K27ac at transcription start sites (TSS) and super-enhancers.”
From HDACs and the epigenetic plasticity of cancer cells: target the complexity (2022) · cites this paper as Caslini et al., 2019
In the citing paper
“Paradoxically, HDAC7 is required to maintain H3K27ac levels at these regulatory elements.”
From HDACs and the epigenetic plasticity of cancer cells: target the complexity (2022) · cites this paper as Caslini et al., 2019
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
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
Super-enhancers in the control of cell identity and disease
Hnisz, D., Abraham, B. J., Lee, T. I., Lau, A., Saint-André, V., Sigova, A. A., Hoke, H. A., & Young, R. A. (2013) · Cell · doi:10.1016/j.cell.2013.09.053 · Cited by 3,662
The Galaxy platform for accessible, reproducible and collaborative biomedical analyses: 2018 update
Afgan, E., Baker, D., Batut, B., van den Beek, M., Bouvier, D., Čech, M., Chilton, J., Clements, D., Coraor, N., Grüning, B. A., et al. (2018) · Nucleic Acids Research · doi:10.1093/nar/gky379 · Cited by 3,662
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
Histone deacetylase inhibitors and the promise of epigenetic (and more) treatments for cancer
Minucci, S., & Pelicci, P. G. (2006) · Nature reviews. Cancer · doi:10.1038/nrc1779 · Cited by 2,234
Erasers of Histone Acetylation: The Histone Deacetylase EnzymesPreprint
Seto, E., & Yoshida, M. (2014) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a018713 · Cited by 2,105
Brainson, C. F., & Kuperwasser, C. (2008) · Breast Cancer Research · doi:10.1186/bcr1982 · Cited by 1,049
Enhancer decommissioning by LSD1 during embryonic stem cell differentiation
Whyte, W. A., Bilodeau, S., Orlando, D. A., Hoke, H. A., Frampton, G. M., Foster, C. T., Cowley, S. M., & Young, R. A. (2012) · Nature · doi:10.1038/nature10805 · Cited by 602
Wilson, A. J., Byun, D.-S., Popova, N., Murray, L. B., L'Italien, K., Sowa, Y., Arango, D., Velcich, A., Augenlicht, L. H., & Mariadason, J. M. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m510023200 · Cited by 575
(2003) · PubMed · Cited by 519
Cited by
Sorted by citations
Modulation of cellular processes by histone and non-histone protein acetylation
Shvedunova, M., & Akhtar, A. (2022) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-021-00441-y · Cited by 1,007
Epigenetic modulation and understanding of HDAC inhibitors in cancer therapy
Ramaiah, M. J., Tangutur, A. D., & Manyam, R. R. (2021) · Life Sciences · doi:10.1016/j.lfs.2021.119504 · Cited by 365
Liquid–liquid phase separation in tumor biology
Tong, X., Tang, R., Xu, J., Wang, W., Zhao, Y., Yu, X., & Shi, S. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-01076-x · Cited by 265
Histone modifications in epigenetic regulation of cancer: Perspectives and achieved progress
Неганова, М. Е., Klochkov, S. G., Aleksandrova, Y. R., & Aliev, G. (2020) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2020.07.015 · Cited by 211
Fatma, H., Maurya, S., & Siddique, H. R. (2020) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2020.11.008 · Cited by 185
Metadata
- Authors
- Caslini, C., Hong, S., Ban, Y. J., Chen, X. S., & Ince, T. A.
- Affiliations
- University of Miami (US)
- Corresponding author
- Caslini, Corrado
- Ince, Tan A.
- Venue
- Oncogene
- Published
- 2019-08-02
- Volume
- 38
- Issue
- 39
- Pages
- 6599-6614
- ISSN
- 0950-9232 (ISSN-L)
- 1476-5594
- OpenAlex
- W2966048051
- Cited by
- 121
- References
- 45
- Citations by year
- 2026: 9 · 2025: 17 · 2024: 19 · 2023: 25 · 2022: 18 · 2021: 21 · 2020: 11
- FWCI
- 4.22
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Oncogene (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Breast Cancer Research Foundation
- Florida Breast Cancer Foundation
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Histone Deacetylase Inhibitors Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Keywords
- HDAC7, HDAC1, HDAC3, histone deacetylase, super-enhancers, breast cancer stem cells, transcriptional regulation, chromatin regulation, transcription start sites, histone deacetylase inhibitors, breast cancer
- MeSH terms
- Histone Deacetylase 3, Acetylation, Benzamides, Breast Neoplasms, Enhancer Elements, Genetic, Female, Histone Deacetylases, Histones, Humans, Lysine, Pyridines, Transcription Factors, Transcription, Genetic, Neoplastic Stem Cells, Down-Regulation, Gene Knockdown Techniques, Histone Deacetylase 1, Histone Deacetylase Inhibitors
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
