{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n KDM4B, also known as JMJD2B, is a Jumonji C‐domain histone demethylase that removes repressive trimethyl marks from lysine 9 of histone H3, thereby promoting transcriptional activation in a variety of biological contexts. In hormone‐responsive cancers such as breast cancer, KDM4B is upregulated by estrogen and hypoxia and is recruited to estrogen receptor α target promoters where it demethylates H3K9me3 to facilitate cell cycle progression and tumor growth (see."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In mesenchymal stem cells, KDM4B plays a critical role in lineage commitment by removing H3K9me3 at promoters of key osteogenic regulators such as DLX, thereby promoting osteogenesis (see."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " In gastric cancer cells, KDM4B promotes epithelial–mesenchymal transition by physically associating with β‐catenin and demethylating the H3K9me3 mark at the promoter of vimentin, which enhances invasive and metastatic properties (see."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " Moreover, in other tumor types including bladder and lung cancers, elevated levels of KDM4B are associated with increased cell proliferation through its regulation of cell cycle effectors such as CDK6 (see."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " In addition to its chromatin‐modifying functions, KDM4B also modulates nonhistone protein methylation; for example, it antagonizes SETDB1‐mediated methylation of AKT, thereby influencing AKT phosphorylation and downstream signaling in oncogenesis (see."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " KDM4B activity further contributes to the maintenance of pluripotency in embryonic stem cells by preserving transcriptional competence through continual demethylation of promoter regions, and it is induced under hypoxic conditions in colorectal cancer cells to drive hypoxia‐responsive gene expression (see."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " Finally, functional redundancy between KDM4B and related isoforms—illustrated by compensation of defects observed in spermatogenesis in the absence of KDM4D—further underscores its versatile role in both developmental and disease processes (see."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Masahito Kawazu, Kayoko Saso, Kit I Tong, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Histone demethylases KDM4B and KDM6B promotes osteogenic differentiation of human MSCs."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Stem Cell (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.stem.2012.04.009"}], "href": "https://doi.org/10.1016/j.stem.2012.04.009"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22770241"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22770241"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Li Zhao, Wenjuan Li, Wen Zang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "JMJD2B promotes epithelial-mesenchymal transition by cooperating with β-catenin and enhances gastric cancer metastasis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Cancer Res (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/1078-0432.CCR-13-0254"}], "href": "https://doi.org/10.1158/1078-0432.CCR-13-0254"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24077348"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24077348"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Gouji Toyokawa, Hyun-Soo Cho, Yukiko Iwai, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The histone demethylase JMJD2B plays an essential role in human carcinogenesis through positive regulation of cyclin-dependent kinase 6."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Prev Res (Phila) (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/1940-6207.CAPR-11-0290"}], "href": "https://doi.org/10.1158/1940-6207.CAPR-11-0290"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21930796"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21930796"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Wenjuan Li, Li Zhao, Wen Zang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Histone demethylase JMJD2B is required for tumor cell proliferation and survival and is overexpressed in gastric cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2011.11.045"}], "href": "https://doi.org/10.1016/j.bbrc.2011.11.045"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22133676"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22133676"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Jianping Guo, Xiangpeng Dai, Benoit Laurent, et al. "}, {"type": "b", "children": [{"type": "t", "text": "AKT methylation by SETDB1 promotes AKT kinase activity and oncogenic functions."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Cell Biol (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41556-018-0261-6"}], "href": "https://doi.org/10.1038/s41556-018-0261-6"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30692625"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30692625"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Partha Pratim Das, Zhen Shao, Semir Beyaz, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Distinct and combinatorial functions of Jmjd2b/Kdm4b and Jmjd2c/Kdm4c in mouse embryonic stem cell identity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.molcel.2013.11.011"}], "href": "https://doi.org/10.1016/j.molcel.2013.11.011"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24361252"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24361252"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Linna Fu, Lisha Chen, Jie Yang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "HIF-1α-induced histone demethylase JMJD2B contributes to the malignant phenotype of colorectal cancer cells via an epigenetic mechanism."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Carcinogenesis (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/carcin/bgs217"}], "href": "https://doi.org/10.1093/carcin/bgs217"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22745382"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22745382"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Naoki Iwamori, Ming Zhao, Marvin L Meistrich, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The testis-enriched histone demethylase, KDM4D, regulates methylation of histone H3 lysine 9 during spermatogenesis in the mouse but is dispensable for fertility."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biol Reprod (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1095/biolreprod.110.088955"}], "href": "https://doi.org/10.1095/biolreprod.110.088955"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21293030"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21293030"}]}]}]}