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KDM6B/JMJD3 histone demethylase is induced by vitamin D and modulates its effects in colon cancer cells
Open accessAbstract
KDM6B/JMJD3 is a histone H3 lysine demethylase with an important gene regulatory role in development and physiology. Here, we show that human JMJD3 expression is induced by the active vitamin D metabolite 1α,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) and that JMJD3 modulates the gene regulatory action of this hormone. 1,25(OH)(2)D(3) activates the JMJD3 gene promoter and increases the level of JMJD3 RNA in human cancer cells. JMJD3 upregulation was strictly dependent on vitamin D receptor (VDR) expression and was abolished by cycloheximide. In SW480-ADH colon cancer cells, JMJD3 knockdown or expression of an inactive mutant JMJD3 fragment decreased the induction by 1,25(OH)(2)D(3) of several target genes and of an epithelial adhesive phenotype. Moreover, JMJD3 knockdown upregulated the epithelial-to-mesenchymal transition inducers SNAIL1 and ZEB1 and the mesenchymal markers fibronectin and LEF1, while it downregulated the epithelial proteins E-cadherin, Claudin-1 and Claudin-7. Additionally, JMJD3 knockdown abolished the nuclear export of β-catenin and the inhibition of β-catenin transcriptional activity caused by 1,25(OH)(2)D(3). Importantly, the expression of JMJD3 correlated directly with that of VDR and inversely with that of SNAI1 in a series of 96 human colon tumours. Our results indicate for the first time that an epigenetic gene coding for a histone demethylase such as JMJD3 is a VDR co-target that partially mediates the effects of 1,25(OH)(2)D(3) on human colon.
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“Regarding epigenetic mechanisms, vitamin D, through its interaction with the vitamin D receptor (VDR), can modulate the activity of chromatin-modifying enzymes, including DNA methyltransferases (DNMTs), histone acetyltransferases (HATs), and histone deacetylases (HDACs).”
From Maternal Overnutrition and Fetal Programming: Long-Term Metabolic, Cognitive, and Epigenetic Consequences (2026) · cites this paper as [152]
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1 retracted
DNA demethylation in hormone-induced transcriptional derepression
Kim, M. S., Kondo, T., Takada, I., Youn, M., Yamamoto, Y., Takahashi, S., Μatsumoto, T., Fujiyama, S., Shirode, Y., Yamaoka, I., et al. (2009) · Nature · doi:10.1038/nature08456 · Cited by 242
RetractedNorman, A. W. (1979) · Cited by 3,769
The Role of Chromatin during Transcription
Li, B., Carey, M., & Workman, J. L. (2007) · Cell · doi:10.1016/j.cell.2007.01.015 · Cited by 3,503
Snail, Zeb and bHLH factors in tumour progression: An alliance against the epithelial phenotype?
Peinado, H., Olmeda, D., & Cano, A. (2007) · Nature reviews. Cancer · doi:10.1038/nrc2131 · Cited by 3,121
Vitamin D signalling pathways in cancer: potential for anticancer therapeutics
Deeb, K. K., Trump, D. L., & Johnson, C. S. (2007) · Nature reviews. Cancer · doi:10.1038/nrc2196 · Cited by 1,419
UTX and JMJD3 are histone H3K27 demethylases involved in HOX gene regulation and development
Agger, K., Cloos, P. A., Christensen, J. F., Pasini, D., Rose, S., Rappsilber, J., Issaeva, I., Canaani, E., Salcini, A. E., & Helin, K. (2007) · Nature · doi:10.1038/nature06145 · Cited by 1,392
Schlesinger, Y., Straussman, R., Keshet, I., Farkash, S., Hecht, M., Zimmerman, J., Eden, E., Yakhini, Z., Ben-Shushan, E., Reubinoff, B. E., et al. (2007) · Nature Genetics · doi:10.1038/ng1950 · Cited by 1,226 · cited 1×
“The presence of H3K27me3 at transcriptional sites usually correlates with gene repression (7,11,12), and Polycomb-mediated H3K27 methylation premarks genes for DNA methylation and silencing in cancer (13).”
BackgroundSystematic sequencing of renal carcinoma reveals inactivation of histone modifying genes
Dalgliesh, G. L., Furge, K., Greenman, C., Chen, L., Bignell, G., Butler, A., Davies, H., Edkins, S., Hardy, C., Latimer, C., et al. (2010) · Nature · doi:10.1038/nature08672 · Cited by 1,173 · cited 1×
“Several KDMs have been implicated in development, differentiation or stem cell renewal, and their mutation or deregulation have been linked to cancer and other diseases (2-7).”
BackgroundCovalent histone modifications — miswritten, misinterpreted and mis-erased in human cancers
Chi, P., Allis, C. D., & Wang, G. G. (2010) · Nature reviews. Cancer · doi:10.1038/nrc2876 · Cited by 1,131
Norman, A. W. (2008) · The American Journal of Clinical Nutrition · doi:10.1093/ajcn/88.2.491s · Cited by 1,090
De Santa, F., Totaro, M. G., Prosperini, E., Notarbartolo, S., Testa, G., & Natoli, G. (2007) · Cell · doi:10.1016/j.cell.2007.08.019 · Cited by 965
Ramagopalan, S. V., Heger, A., Berlanga‐Taylor, A. J., Maugeri, N., Lincoln, M. R., Burrell, A., Handunnetthi, L., Handel, A. E., Disanto, G., Orton, S. M., et al. (2010) · Genome Research · doi:10.1101/gr.107920.110 · Cited by 881
Snail blocks the cell cycle and confers resistance to cell deathPreprint
Vega, S., Morales, A. V., Ocaña, O. H., Valdés, F., Fabregat, I., & Nieto, M. A. (2004) · Genes & Development · doi:10.1101/gad.294104 · Cited by 866
A histone H3 lysine 27 demethylase regulates animal posterior development
Lan, F., Bayliss, P. E., Rinn, J. L., Whetstine, J. R., Wang, J. K., Chen, S., Iwase, S., Alpatov, R., Issaeva, I., Canaani, E., et al. (2007) · Nature · doi:10.1038/nature06192 · Cited by 808
Pálmer, H. G., González‐Sancho, J. M., Espada, J., Berciano, M. T., Puig, I., Baulida, J., Quintanilla, M., Cano, A., de Herreros, A. G., Lafarga, M., et al. (2001) · The Journal of Cell Biology · doi:10.1083/jcb.200102028 · Cited by 803
Demethylation of H3K27 Regulates Polycomb Recruitment and H2A Ubiquitination
Lee, M. G., Villa, R., Trojer, P., Norman, J. A., Yan, K.-P., Reinberg, D., Croce, L. D., & Shiekhattar, R. (2007) · Science · doi:10.1126/science.1149042 · Cited by 789
Somatic mutations of the histone H3K27 demethylase gene UTX in human cancer
van Haaften, G., Dalgliesh, G. L., Davies, H., Chen, L., Bignell, G., Greenman, C., Edkins, S., Hardy, C., O'Meara, S., Teague, J., et al. (2009) · Nature Genetics · doi:10.1038/ng.349 · Cited by 784
Gadd45a promotes epigenetic gene activation by repair-mediated DNA demethylation
Barreto, G., Schäfer, A., Marhold, J., Stach, D., Swaminathan, S. K., Handa, V., Doederlein, G., Maltry, N., Wu, W., Lyko, F., et al. (2007) · Nature · doi:10.1038/nature05515 · Cited by 771
Identification of JmjC domain-containing UTX and JMJD3 as histone H3 lysine 27 demethylases
Hong, S., Cho, Y., Yu, L., Yu, H., Veenstra, T. D., & Ge, K. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0707292104 · Cited by 716
Wang, T. T., Tavera-Mendoza, L. E., Laperrière, D., Libby, E., MacLeod, N. B., Nagai, Y., Bourdeau, V., Konstorum, A., Lallemant, B., Zhang, R., et al. (2005) · Molecular Endocrinology · doi:10.1210/me.2005-0106 · Cited by 577
Insights from genomic profiling of transcription factors
Farnham, P. J. (2009) · Nature Reviews Genetics · doi:10.1038/nrg2636 · Cited by 519
Yamane, K., Tateishi, K., Klose, R. J., Fang, J., Fabrizio, L. A., Erdjument‐Bromage, H., Taylor‐Papadimitriou, J., Tempst, P., & Zhang, Y. (2007) · Molecular Cell · doi:10.1016/j.molcel.2007.03.001 · Cited by 505
García-Bassets, I., Kwon, Y., Telese, F., Préfontaine, G. G., Hutt, K. R., Cheng, C. S., Ju, B., Ohgi, K. A., Wang, J., Escoubet‐Lozach, L., et al. (2007) · Cell · doi:10.1016/j.cell.2006.12.038 · Cited by 438
Jmjd3 contributes to the control of gene expression in LPS‐activated macrophages
Santa, F. D., Narang, V., Yap, Z. H., Tusi, B. K., Burgold, T., Austenaa, L. M. I., Bucci, G., Cagánová, M., Notarbartolo, S., Casola, S. S., et al. (2009) · The EMBO Journal · doi:10.1038/emboj.2009.271 · Cited by 433
Agger, K., Cloos, P. A. C., Rudkjær, L., Williams, K., Andersen, G., Christensen, J., & Helin, K. (2009) · Genes & Development · doi:10.1101/gad.510809 · Cited by 427
Histone demethylase JMJD3 contributes to epigenetic control of INK4a/ARF by oncogenic RAS
Barradas, M., Anderton, E., Acosta, J. C., Li, S., Banito, A., Rodriguez-Niedenführ, M., Maertens, G., Banck, M., Zhou, M.-M., Walsh, M. J., et al. (2009) · Genes & Development · doi:10.1101/gad.511109 · Cited by 352
Bouillon, R., Eelen, G., Verlinden, L., Mathieu, C., Carmeliet, G., & Verstuyf, A. (2006) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2006.09.014 · Cited by 350
H3K27 Demethylases, at Long Last
Swigut, T., & Wysocka, J. (2007) · Cell · doi:10.1016/j.cell.2007.09.026 · Cited by 327
Histone H4K20/H3K9 demethylase PHF8 regulates zebrafish brain and craniofacial development
Qi, H. H., Sarkissian, M., Hu, G., Wang, Z., Bhattacharjee, A., Gordon, D. B., Gonzales, M., Lan, F., Ongusaha, P. P., Huarte, M., et al. (2010) · Nature · doi:10.1038/nature09261 · Cited by 305
The emerging field of dynamic lysine methylation of non-histone proteins
Huang, J. L., & Berger, S. L. (2008) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2008.01.012 · Cited by 296
Pálmer, H. G., Larriba, M. J., García, J. M., Ordóñez‐Morán, P., Peña, C., Peiró, S., Puig, I., Rodríguez, R., de la Fuente, R., Bernad, A., et al. (2004) · Nature Medicine · doi:10.1038/nm1095 · Cited by 286
Self-citationBlockade of Wnt/β-Catenin Signaling by Paricalcitol Ameliorates Proteinuria and Kidney Injury
He, W., Kang, Y. S., Dai, C., & Liu, Y. (2010) · Journal of the American Society of Nephrology · doi:10.1681/asn.2009121236 · Cited by 258
Saramaki, A. (2006) · Nucleic Acids Research · doi:10.1093/nar/gkj460 · Cited by 252
The Molecular Basis of Vitamin D Receptor and β-Catenin Crossregulation
Shah, S., Islam, M. N., Dakshanamurthy, S., Rizvi, I., Rao, M., Herrell, R., Zinser, G. M., Valrance, M., Aranda, A., Moras, D., et al. (2006) · Molecular Cell · doi:10.1016/j.molcel.2006.01.037 · Cited by 244
Developmental roles of the histone lysine demethylases
Nottke, A. C., Colaiácovo, M. P., & Shi, Y. (2009) · Development · doi:10.1242/dev.020966 · Cited by 229
The Role of Vitamin D in Cancer Prevention and Treatment
Krishnan, A. V., Trump, D. L., Johnson, C. S., & Feldman, D. (2010) · Endocrinology and Metabolism Clinics of North America · doi:10.1016/j.ecl.2010.02.011 · Cited by 199
Peña, C., García, J. M., Silva, J., García‐Barberán, V., Rodríguez, R., Alonso, I., Millán, I., Salas, C., de Herreros, A. G., Múñoz, A., et al. (2005) · Human Molecular Genetics · doi:10.1093/hmg/ddi366 · Cited by 191
Self-citationHeterochromatic Genome Stability Requires Regulators of Histone H3 K9 Methylation
Peng, J. C., & Karpen, G. H. (2009) · PLoS Genetics · doi:10.1371/journal.pgen.1000435 · Cited by 183
The vitamin D receptor in cancer
Thorne, J. L., & Campbell, M. J. (2008) · Proceedings of The Nutrition Society · doi:10.1017/s0029665108006964 · Cited by 152
Self-citationAnderton, J. A., Bose, S., Vockerodt, M., Vrzalikova, K., Wei, W., Kuo, M., Helin, K., Christensen, J. F., Rowe, M., Murray, P. G., et al. (2011) · Oncogene · doi:10.1038/onc.2010.579 · Cited by 144
Vaïsänen, S., Dunlop, T. W., Sinkkonen, L., Frank, C., & Carlberg, C. (2005) · Journal of Molecular Biology · doi:10.1016/j.jmb.2005.04.057 · Cited by 139
Cystatin D is a candidate tumor suppressor gene induced by vitamin D in human colon cancer cells
Álvarez-Díaz, S., Valle, N., García, J. M., Peña, C., Freije, J. M. P., Quesada, V., Astudillo, A., Bonilla, F., López-Otín, C., & Múñoz, A. (2009) · Journal of Clinical Investigation · doi:10.1172/jci37205 · Cited by 135
Self-citationSnail2 cooperates with Snail1 in the repression of vitamin D receptor in colon cancer
Larriba, M. J., Martín-Villar, E., Garcia, J. M., Pereira, F., Peña, C., de Herreros, A. G., Bonilla, F., & Munoz, A. (2009) · Carcinogenesis · doi:10.1093/carcin/bgp140 · Cited by 130
Self-citationVitamin D regulates the phenotype of human breast cancer cells
Pendás-Franco, N., González‐Sancho, J. M., Suárez, Y., Aguilera, O., Steinmeyer, A., Gamallo, C., Berciano, M. T., Lafarga, M., & Múñoz, A. (2006) · Differentiation · doi:10.1111/j.1432-0436.2006.00131.x · Cited by 127
Nuclear receptors: Genomic and non-genomic effects converge
Ordóñez‐Morán, P., & Múñoz, A. (2009) · Cell Cycle · doi:10.4161/cc.8.11.8579 · Cited by 120
Ordóñez‐Morán, P., Larriba, M. J., Pálmer, H. G., Valero, R. A., Barbáchano, A., Duñach, M., de Herreros, A. G., Villalobos, C., Berciano, M. T., Lafarga, M., et al. (2008) · The Journal of Cell Biology · doi:10.1083/jcb.200803020 · Cited by 116
Self-citationA genomic perspective on vitamin D signaling.
Carlberg, C., & Seuter, S. (2009) · PubMed · Cited by 109
Regulation of multiple insulin-like growth factor binding protein genes by 1 ,25-dihydroxyvitamin D3
Matilainen, M. (2005) · Nucleic Acids Research · doi:10.1093/nar/gki872 · Cited by 100
Larriba, M. J., Valle, N., Pálmer, H. G., Ordóñez‐Morán, P., Álvarez-Díaz, S., Becker, K., Gamallo, C., de Herreros, A. G., González‐Sancho, J. M., & Múñoz, A. (2007) · Endocrine Related Cancer · doi:10.1677/erc-06-0028 · Cited by 95
Self-citationGenome-wide principles of gene regulation by the vitamin D receptor and its activating ligand
Pike, J. W. (2011) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2011.05.012 · Cited by 83
Egan, J. B., Thompson, P. A., Vitanov, M., Bartik, L., Jacobs, E. T., Haussler, M. R., Gerner, E. W., & Jurutka, P. W. (2009) · Molecular Carcinogenesis · doi:10.1002/mc.20603 · Cited by 76
Thorne, J. L., Maguire, O., Doig, C. L., Battaglia, S., Fehr, L., Sucheston, L. E., Heinäniemi, M., O’Neill, L. P., McCabe, C. J., Turner, B. M., et al. (2010) · Nucleic Acids Research · doi:10.1093/nar/gkq875 · Cited by 73
Self-citationMeta-analysis of primary target genes of peroxisome proliferator-activated receptors
Heinäniemi, M., Uski, J. O., Degenhardt, T., & Carlberg, C. (2007) · Genome Biology · doi:10.1186/gb-2007-8-7-r147 · Cited by 71
Minireview: Role of Protein Methylation and Demethylation in Nuclear Hormone Signaling
Wu, S. C., & Zhang, Y. (2009) · Molecular Endocrinology · doi:10.1210/me.2009-0131 · Cited by 52
Vitamin D receptor modulates the neoplastic phenotype through antagonistic growth regulatory signals
Xu, H., McCann, M., Zhang, Z., Posner, G. H., Bingham, V., El‐Tanani, M., & Campbell, F. C. (2009) · Molecular Carcinogenesis · doi:10.1002/mc.20520 · Cited by 34
The Epidemiology of Vitamin D and Cancer Risk
Giovannucci, E. L. (2009) · Clinical Reviews in Bone and Mineral Metabolism · doi:10.1007/s12018-009-9030-1 · Cited by 14
The Epidemiology of Vitamin D and Cancer Risk
Giovannucci, E. L. (2011) · Elsevier eBooks · doi:10.1016/b978-0-12-381978-9.10082-4 · Cited by 3
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Metadata
- Authors
- Pereira, F., Barbáchano, A., Silva, J., Bonilla, F., Campbell, M. J., Muñoz, A., & Larriba, M. J.
- Affiliations
- Consejo Superior de Investigaciones Científicas (ES)
- Hospital Universitario Puerta de Hierro Majadahonda (ES)
- Roswell Park Comprehensive Cancer Center (US)
- Venue
- Human Molecular Genetics
- Publisher
- Oxford University Press (OUP)
- Published
- 2011-09-02
- Volume
- 20
- Issue
- 23
- Pages
- 4655-4665
- ISSN
- 0964-6906 (ISSN-L)
- 1460-2083
- OpenAlex
- W2130478754
- Cited by
- 177
- References
- 57
- Citations by year
- 2026: 5 · 2025: 12 · 2024: 6 · 2023: 7 · 2022: 27 · 2021: 14 · 2020: 11 · 2019: 14 · 2018: 16 · 2017: 12 · 2016: 9 · 2015: 9 · 2014: 14 · 2013: 11 · 2012: 9
- FWCI
- 4.55
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Licence
- other-oa
- Locations
- Human Molecular Genetics (publishedVersion)
- PubMed (publishedVersion)
- DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion, other-oa)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Vitamin D Research Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- vitamin D, 1,25-dihydroxyvitamin D3, vitamin D receptor, colon cancer, epithelial-mesenchymal transition, SNAI1, ZEB1, E-cadherin, claudin-1, claudin-7, gene expression regulation, epigenetic regulation
- MeSH terms
- Snail Family Transcription Factors, Calcitriol, Colonic Neoplasms, Enzyme Induction, Humans, Transcription Factors, Vitamin D, Transcriptional Activation, Gene Expression Regulation, Neoplastic, Receptors, Calcitriol, Cell Line, Tumor, Cell Proliferation, Gene Knockdown Techniques, Jumonji Domain-Containing Histone Demethylases, Epithelial-Mesenchymal Transition, Wnt Signaling Pathway
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