KDM3B Is the H3K9 Demethylase Involved in Transcriptional Activation of lmo2 in Leukemia
Open accessAbstract
Histone lysine methylation and demethylation are considered critical steps in transcriptional regulation. In this report, we performed chromatin immunoprecipitation with microarray technology (ChIP-chip) analysis to examine the genome-wide occupancy of H3K9-me2 during all-trans-retinoic acid (ATRA)-induced differentiation of HL-60 promyelocytic leukemia cells. Using this approach, we found that KDM3B, which contains a JmjC domain, was downregulated during differentiation through the recruitment of a corepressor complex. Furthermore, KDM3B displayed histone H3K9-me1/2 demethylase activity and induced leukemogenic oncogene lmo2 expression via a synergistic interaction with CBP. Here, we found that KDM3B repressed leukemia cell differentiation and was upregulated in blood cells from acute lymphoblastic leukemia (ALL)-type leukemia patients. The combined results of this study provide evidence that the H3K9-me1/2 demethylase KDM3B might play a role in leukemogenesis via activation of lmo2 through interdependent actions with the histone acetyltransferase (HAT) complex containing CBP.
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KDM3B is a JumonjiC domain-containing histone demethylase with specificity toward H3K9 and is involved in gene activation in leukemia cells.
“KDM3B was recently characterized as a member of the JumonjiC domain-containing histone demethylases that shows specificity toward H3K9 and is involved gene activation in leukemia cells [25, 26]”
From Histone H3 lysine-to-methionine mutants as a paradigm to study chromatin signaling (2014) · cites this paper as [26]
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“Interestingly, KDM3B was recently identified to interact with CBP in a yeast 2hybrid screen and was reported to act synergistically with CBP to repress ATRA-induced differentiation of leukemia cells (Kim et al., 2012).”
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“KDM3B 51780 Lysine demethylase 3b Demethylase (43)”
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BackgroundInfluentialSelf-citationThe Molecular Basis of Histone Demethylation
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The emerging roles for histone demethylases in the modulation of signaling pathways
Stefano, L. D., & Dyson, N. J. (2012) · BioMolecular Concepts · doi:10.1515/bmc-2012-0031 · Cited by 6 · see citing works
Song, Y. Q., Zhang, J., Wang, H., Wang, H., Liu, Y., & Hu, Z. (2023) · International Journal of Oncology · doi:10.3892/ijo.2023.5535 · Cited by 5 · see citing works
Jung, H., & Seo, S. (2020) · PLoS ONE · doi:10.1371/journal.pone.0236403 · Cited by 7 · see citing works
“KDM3B could regulate the expression of leukemogenic lmo2 by reducing H3K9me2 on the promoter in HL-60, which are acute promyelocytic leukemia cells [18].”
BackgroundSelf-citationThe role of epigenetic modifications in hematological cancers
Ilic, J., Bold, A., & Knop, S. T. (2026) · Frontiers in Oncology · doi:10.3389/fonc.2026.1744018 · Cited by 4 · see citing works
“In ALL, the histone methyltransferase KDM2B is upregulated, acting cooperatively with HATs to induce oncogene expression (165).”
Unraveling the Role of JMJD1B in Genome Stability and the Malignancy of Melanomas
Cruz, P., Peña-Lopez, D., Figueroa, D., Riobó, I., Benedetti, V., Saavedra, F., Espinoza-Arratia, C., Escobar, T., Lladser, Á., & Loyola, A. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms251910689 · Cited by 4
“While the H3K9 demethylation mediated by JMJD1B has been recognized for its impact on gene expression and cancer development [21,22,29,30,33–35], our results demonstrate that the absence of JMD1B also contributes to genome instability through the deregulation of histone distribution and delivery to…”
BackgroundThe histone demethylase Kdm3 prevents auto-immune piRNAs production in Drosophila
Casier, K., Autaa, J., Gueguen, N., Delmarre, V., Marie, P. P., Ronsseray, S., Carré, C., Brasset, É., Teysset, L., & Boivin, A. (2023) · Science Advances · doi:10.1126/sciadv.ade3872 · Cited by 13 · see citing works
“KDM3B is involved in gene activation in leukemia cells ( 26 , 27 ); for review, see ( 28 ).”
Jung, H., Kim, J., Kim, K., Chae, Y., Hahn, Y., Kim, J.-W., & Seo, S. (2018) · PLoS ONE · doi:10.1371/journal.pone.0202935 · Cited by 5 · see citing works
Self-citationHistone Demethylases in Prostate Cancer
Wang, L., Guo, W., Kim, K., Pochampalli, M. R., Hung, C.-L., Izumiya, Y., & Kung, H.-J. (2013) · Cancer drug discovery and develogment/Cancer drug discovery and development · doi:10.1007/978-1-4614-8039-6_15 · Cited by 3 · see citing works
Self-citationHong, Y., Guo, H., Chen, Q., & Yu, C. (2026) · Molecular Biomedicine · doi:10.1186/s43556-026-00434-3 · Cited by 3 · see citing works
“JMJD1B displays a dual role, acting as an oncogene by activating LMO2 in acute lymphoblastic leukemia (ALL) [280], but showing tumor-suppressive activity in specific AML contexts, notably in subtypes with MLL-AF6/9 or PML-RARα rearrangements, as well as in acute pro-myelocytic leukemia (APL), where…”
Karpenko, A. R., Kobzeva, K., Orlov, Y., & Bushueva, O. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26188967 · Cited by 3 · see citing works
“Upregulation of KDM3B , a histone H3K9 demethylase, can result in dysregulation of the cell cycle and cell proliferation [82,83], whereas downregulation of ETF1 , a protein crucial for the termination of RNA translation [84], may impact the synthesis of viral proteins, including SARS-CoV-2 in host…”
Lysine demethylases and cancer
Eckschlager, T., Vícha, A., & Frolikova, D. (2025) · Pathology - Research and Practice · doi:10.1016/j.prp.2025.156011 · Cited by 2 · see citing works
Olofinsae, S. A., Ibeh, B. O., & Ahluwalia, J. (2014) · Asian Pacific Journal of Tropical Medicine · doi:10.1016/s1995-7645(14)60245-5 · Cited by 2 · see citing works
“Generally, CD14 mRNA have been reported to increase in a time- and dose-dependent manner when treated with calcitriol[40]; this may suggest that only calcitriol could induce differentiation of U937 cells along monocytic pathway.”
BackgroundNovel Therapeutics Targeting Epigenetics
Woster, P. M. (2017) · Elsevier eBooks · doi:10.1016/b978-0-12-409547-2.12325-x · Cited by 1 · see citing works
Jo, S., Lee, C., White, L., Shillington, A., Slavotinek, A., & Wu, Y.-N. (2025) · Clinical Genetics · doi:10.1111/cge.70107 · Cited by 1
An, M.-J., Kim, J., Park, J., Kim, J., Kim, D., Shin, G.-S., Lee, H., Jo, A.-R., Kim, C.-H., Kim, M. J., et al. (2022) · Research Square · doi:10.21203/rs.3.rs-1246914/v1 · Cited by 1 · see citing works
Self-citationA rare rearrangement of 5q31.2 in a child with a neurodevelopmental syndrome
Goldenstein, H., Shrem, S. B., Weiss, O., Zeligson, S., Segel, R., Mory, A., & Weiss, K. (2021) · Clinical Dysmorphology · doi:10.1097/mcd.0000000000000380 · Cited by 1 · see citing works
Zhu, Z., Wu, X.-L., Li, Q., Zhang, J.-Q., Yu, S., Shen, Q., Zhou, Z., Pan, Q., Yue, W., Qin, D., et al. (2020) · doi:10.1101/2020.08.16.245639 · Cited by 1
“The conventional view is that KDM3A 388 and KDM3B may function in a redundant manner [8-10].”
BackgroundDynamic regulation of H3K9 modifications in cancer: pathogenesis and targeted therapies
Xu, Y., Wu, Q., Zhang, Y., Zhao, J., Fu, X., Li, A., & Li, Y. (2026) · Biomarker Research · doi:10.1186/s40364-026-01019-6
“KDM3B exhibits opposing functions in hematological malignancies: it cooperates with CBP to activate LMO2 and promote leukemogenesis [212], whereas tumor-suppressive effects have been reported in AML and acute promyelocytic leukemia, where KDM3B restricts malignant proliferation and supports…”
Suman, M., Hallén, T., Garner, T., Thorsell, A., Stevens, A., Köster, L., Carén, H., Ragnarsson, Ó., Skoglund, T. S., & Johannsson, G. (2026) · Journal of Translational Medicine · doi:10.1186/s12967-026-08495-2
“• Acts as oncogene in prostate cancer [58], hepatocellular carcinoma [59], renal cell carcinoma [60], and acute lymphoblastic leukemia [61] promoting cell proliferation 12 B5ME19 EIF3CL Yes, p = 1.3e-06 Protein synthesis • Overexpressed in diffuse intrinsic pontine glioma and associated with cell…”
MATR3 is essential for oocyte growth and maturation quality through a dual molecular mechanism
Bao, Y.-B., Zuo, Z.-Z., Wang, T.-T., Lin, L., Gao, M., Qin, S.-G., Yang, Q., Liu, B.-Y., Sun, W.-Y., Ma, J., et al. (2026) · bioRxiv · doi:10.64898/2026.02.12.705648
“Given its functional conservation and central role in oocyte maturation, MATR3 represents a promising diagnostic marker and therapeutic target for clinical OMA.”
[A case report of Diets-Jongmans syndrome caused by a KDM3B gene variant].
Shen, K., Xiang, Y., Wang, J., Ren, K., & Ding, Y. (2026) · Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · doi:10.7499/j.issn.1008-8830.2508138
Miao, H., Zhang, T., Chen, S., Xu, X.-C., Fang, K.-X., Wu, D.-W., Zhang, Y., & Huang, X.-W. (2026) · Genes · doi:10.3390/genes17030294
Zhu, L.-P., Peng, X.-Y., Yu, H., Fan, X., & Ye, Z.-J. (2026) · BioMed Research International · doi:10.1155/bmri/6916290
“Studies have confirmed that TMB and MSI are closely correlated with the efficacy of ICBs [9, 53, 54].”
InfluentialNovel KDM3B Variants in Two Chinese Patients With Global Developmental Delay and Autism
Cao, F., Xiong, L., Wu, H.-P., Chen, Y., & Zha, J. (2025) · International Journal of Developmental Neuroscience · doi:10.1002/jdn.70077
KDM3A and KDM3B Maintain Naïve Pluripotency Through the Regulation of Alternative SplicingPreprint
Dillingham, C. M., Cormaty, H., Morgan, E. C., Tak, A. I., Esgdaille, D. E., Boutz, P. L., & Sridharan, R. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.05.31.543088 · Cited by 1 · see citing works
Jupe, S. (2014) · doi:10.3180/react_228178.1
- Authors
- Kim, J.-Y., Kim, K.-B., Eom, G. H., Choe, N., Kee, H. J., Son, H.-J., Oh, S.-T., Kim, D.-W., Pak, J. H., Baek, H. J., Kook, H., Hahn, Y., Kook, H., Chakravarti, D., & Seo, S.-B.
- Affiliations
- Chung-Ang University (KR)
- Chonnam National University (KR)
- Jeonbuk National University (KR)
- Asan Medical Center (KR)
- Chonnam National University Hwasun Hospital (KR)
- Northwestern University (US)
- ORCID
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 2012-07-01
- Volume
- 32
- Issue
- 14
- Pages
- 2917-2933
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- PMC
- PMC3416203
- OpenAlex
- W2149375432
- Cited by
- 115
- References
- 0
- Citations by year
- 2026: 11 · 2025: 7 · 2024: 11 · 2023: 8 · 2022: 6 · 2021: 11 · 2020: 9 · 2019: 8 · 2018: 8 · 2017: 8 · 2016: 3 · 2015: 7 · 2014: 9 · 2013: 7 · 2012: 2
- FWCI
- 3.22
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Molecular and Cellular Biology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of Birmingham
- Korea Basic Science Institute
- National Research Foundation of Korea
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cancer-related gene regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- KDM3B, H3K9 methylation, LMO2, leukemia, acute lymphoblastic leukemia, promyelocytic leukemia, CBP, histone acetyltransferase complexes, histone demethylation, transcriptional activation, leukemogenesis, JmjC domain, corepressor complex
- MeSH terms
- Base Sequence, Cell Differentiation, DNA, Neoplasm, Histones, Humans, Neoplasm Proteins, Oncogenes, Promoter Regions, Genetic, Proto-Oncogene Proteins, Recombinant Proteins, Tretinoin, Leukemia, Promyelocytic, Acute, Transcriptional Activation, Gene Expression Regulation, Leukemic, HL-60 Cells, K562 Cells, Oligonucleotide Array Sequence Analysis, Adaptor Proteins, Signal Transducing, Histone Acetyltransferases, Jumonji Domain-Containing Histone Demethylases, HEK293 Cells, LIM Domain Proteins
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