The DOI matches its Crossref record; 57 of the 57 references it cites were found in a registry or an index.
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
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Inhibitors of Protein Methyltransferases and Demethylases
Kanıskan, H. Ü., Martini, M. L., & Jin, J. J. (2017) · Chemical Reviews · doi:10.1021/acs.chemrev.6b00801 · Cited by 327
Fetahu, I. S., Höbaus, J., & Kállay, E. (2014) · Frontiers in Physiology · doi:10.3389/fphys.2014.00164 · Cited by 313
An Update on Vitamin D Metabolism
Saponaro, F., Saba, A., & Zucchi, R. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21186573 · Cited by 339
An update on vitamin D signaling and cancer
Carlberg, C., & Múñoz, A. (2020) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2020.05.018 · Cited by 298
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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