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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.
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“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
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“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
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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
Upregulation and Nuclear Recruitment of HDAC1 in Hormone Refractory Prostate Cancer
Halkidou, K., Gaughan, L., Cook, S., Leung, H. Y., Neal, D. E., & Robson, C. N. (2004) · The Prostate · doi:10.1002/pros.20022 · Cited by 515
Pasini, D., Malatesta, M., Jung, H. R., Walfridsson, J., Willer, A., Olsson, L., Skotte, J., Wutz, A., Porse, B. T., Jensen, O. N., et al. (2010) · Nucleic Acids Research · doi:10.1093/nar/gkq244 · Cited by 413
Li, B., Samanta, A., Song, X., Iacono, K. T., Bembas, K., Tao, R. N., Basu, S., Riley, J. L., Hancock, W. W., Shen, Y., et al. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0700298104 · Cited by 410
Chromatin repressive complexes in stem cells, development, and cancer
Laugesen, A., & Helin, K. (2014) · Cell stem cell · doi:10.1016/j.stem.2014.05.006 · Cited by 352
Hull, E. E., Montgomery, M. R., & Leyva, K. J. (2016) · BioMed Research International · doi:10.1155/2016/8797206 · Cited by 319
Transformation of Different Human Breast Epithelial Cell Types Leads to Distinct Tumor Phenotypes
Ince, T. A., Richardson, A. L., Bell, G. W., Saitoh, M., Godár, S., Karnoub, A. E., Iglehart, J. D., & Weinberg, R. A. (2007) · Cancer Cell · doi:10.1016/j.ccr.2007.06.013 · Cited by 310
Self-citationRepression of transcription of the p27Kip1 cyclin-dependent kinase inhibitor gene by c-Myc
Yang, W. E., Shen, J., Wu, M., Arsura, M., Fitzgerald, M. J., Suldan, Z., Kim, D. W., Hofmann, C. S., Pianetti, S., Romieu, R., et al. (2001) · Oncogene · doi:10.1038/sj.onc.1204245 · Cited by 277
Human HDAC7 Histone Deacetylase Activity Is Associated with HDAC3in Vivo
Fischle, W., Dequiedt, F., Fillion, M., Hendzel, M. J., Voelter, W., & Verdin, E. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m104935200 · Cited by 232
Mechanism for Nucleocytoplasmic Shuttling of Histone Deacetylase 7
Kao, H., Verdel, A., Tsai, C., Simon, C. M., Juguilon, H., & Khochbin, S. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m107631200 · Cited by 226
A Dynamic Role for HDAC7 in MEF2-mediated Muscle Differentiation
Dressel, U., Bailey, P. J., Wang, S.-C., Downes, M., Evans, R. M., & Muscat, G. E. O. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m101508200 · Cited by 212
Kato, H., Tamamizu‐Kato, S., & Shibasaki, F. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m406320200 · Cited by 202
Histone Deacetylases Positively Regulate Transcription through the Elongation Machinery
Greer, C. B., Tanaka, Y., Kim, Y. J., Xie, P., Zhang, M. Q., Park, I.-H., & Kim, T. H. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.10.013 · Cited by 174
Witt, A. E., Lee, C.-W., Lee, T. I., Azzam, D. J., Wang, B., Caslini, C., Petrocca, F., Grosso, J., Jones, M., Cohick, E. B., et al. (2017) · Oncogene · doi:10.1038/onc.2016.337 · Cited by 172
Self-citationEnhancer Logic and Mechanics in Development and Disease
Rickels, R. A., & Shilatifard, A. (2018) · Trends in Cell Biology · doi:10.1016/j.tcb.2018.04.003 · Cited by 171
Jensen, E. D., Schroeder, T. M., Bailey, J., Gopalakrishnan, R., & Westendorf, J. J. (2007) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.071104 · Cited by 158
Hdac7 promotes lung tumorigenesis by inhibiting Stat3 activation
Lei, Y., Liu, L., Zhang, S., Guo, S., Li, X., Wang, J., Su, B., Fang, Y., Chen, X., Ke, H., et al. (2017) · Molecular Cancer · doi:10.1186/s12943-017-0736-2 · Cited by 152
Self-citationTip60 Is a Co-repressor for STAT3
Xiao, H., Chung, J., Kao, H., & Yang, Y. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m210816200 · Cited by 122
Histone modifications silence the GATA transcription factor genes in ovarian cancer
Caslini, C., Capo‐chichi, C. D., Roland, I., Nicolas, É., Yeung, A. T., & Xx, X. (2006) · Oncogene · doi:10.1038/sj.onc.1209533 · Cited by 107
Self-citationNeuroprotection by histone deacetylase-related protein
Morrison, B. E., Majdzadeh, N., Zhang, X., Lyles, A., Bassel-Duby, R., Olson, E. N., & D'Mello, S. R. (2006) · Molecular and Cellular Biology · doi:10.1128/mcb.26.9.3550-3564.2006 · Cited by 100
Histone deacetylase inhibitors selectively suppress expression of HDAC7
Dokmanovic, M., Perez, G., Xu, W., Ngo, L., Clarke, C., Parmigiani, R. B., & Marks, P. A. (2007) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-07-0251 · Cited by 99
Kim, Y. J., Greer, C. B., Cecchini, K. R., Harris, L. N., Tuck, D. P., & Kim, T. H. (2013) · Oncogene · doi:10.1038/onc.2013.32 · Cited by 95
Sanchez, G. J., Richmond, P. A., Bunker, E. N., Karman, S. S., Azofeifa, J. G., Garnett, A. T., Xu, Q., Wheeler, G. E., Toomey, C. M., Zhang, Q., et al. (2017) · Nucleic Acids Research · doi:10.1093/nar/gkx1225 · Cited by 92
Ma, C., & D’Mello, S. R. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.146860 · Cited by 83
Histone Deacetylase 7 and FoxA1 in Estrogen-Mediated Repression of RPRM
Malik, S., Jiang, S., Garee, J. P., Verdin, E. M., Lee, A. V., O’Malley, B. W., Zhang, M., Belaguli, N. S., & Oesterreich, S. (2009) · Molecular and Cellular Biology · doi:10.1128/mcb.00907-09 · Cited by 79
Effects of novel HDAC inhibitors on urothelial carcinoma cells
Kaletsch, A., Pinkerneil, M., Hoffmann, M. J., Vasudevan, A. A. J., Wang, C., Hansen, F. K., Wiek, C., Hanenberg, H., Gertzen, C. G. W., Gohlke, H., et al. (2018) · Clinical Epigenetics · doi:10.1186/s13148-018-0531-y · Cited by 77
Histone H4 acetylation and histone deacetylase 1 expression in esophageal squamous cell carcinoma
Toh, Y., Yamamoto, M., Endo, K., Ikeda, Y., Baba, H., Kohnoe, S., Yonemasu, H., Hachitanda, Y., Okamura, T., & Sugimachi, K. (2003) · Oncology Reports · doi:10.3892/or.10.2.333 · Cited by 73
The role of histone deacetylase 7 (HDAC7) in cancer cell proliferation: regulation on c-Myc
Zhu, C.-H., Chen, Q., Xie, Z., Ai, J., Tong, L., Ding, J., & Geng, M. (2010) · Journal of Molecular Medicine · doi:10.1007/s00109-010-0701-7 · Cited by 65
Singh, J., Murata, K., Itahana, Y., & Desprez, P. Y. (2002) · Oncogene · doi:10.1038/sj.onc.1205252 · Cited by 63
Barneda‐Zahonero, B., Collazo, O., Azagra, A., Fernández-Duran, I., Serra-Musach, J., Islam, A. B. M. M. K., Vega‐García, N., Malatesta, R., Camós, M., Gómez, A., et al. (2015) · Cell Death and Disease · doi:10.1038/cddis.2014.594 · Cited by 61
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Aude‐Garcia, C., Collin‐Faure, V., Bausinger, H., Hanau, D., Rabilloud, T., & Lemercier, C. (2010) · Biochemical Journal · doi:10.1042/bj20100131 · Cited by 58
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Ai, W., Zheng, H., Yang, X., Liu, Y., & Wang, T. C. (2007) · Nucleic Acids Research · doi:10.1093/nar/gkm656 · Cited by 48
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Yano, M., Yasuda, M., Sakaki, M., Nagata, K., Fujino, T., Arai, E., Hasebe, T., Miyazawa, M., Miyazawa, M., Ogane, N., et al. (2018) · Oncology Letters · doi:10.3892/ol.2018.7726 · Cited by 48
Ahn, M., & Yoon, J. (2017) · Journal of Oral Pathology and Medicine · doi:10.1111/jop.12560 · Cited by 47
MiR-489 suppresses tumor growth and invasion by targeting HDAC7 in colorectal cancer
Gao, S., Liu, H., Hou, S., Wu, L., Yang, Z., Shen, J., Zhou, L., Zheng, S., & Jiang, B. (2017) · Clinical & Translational Oncology · doi:10.1007/s12094-017-1770-7 · Cited by 38
Yu, Y., Cao, F., Yu, X., Zhou, P., Di, Q., Lei, J., Tai, Y., Wu, H., Li, X., Wang, X., et al. (2017) · Clinical & Translational Oncology · doi:10.1007/s12094-017-1639-9 · Cited by 36
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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
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