Abstract
Arising from L. Kruidenier et al. Nature 488, 404–408 (2012); doi:10.1038/nature11262
The recent publication1 of the first highly potent and specific inhibitor GSK-J1/J4 of the H3K27me3/me2-demethylases JMJD3/KDM6B and UTX/KDM6A provides a potential tool compound for this histone demethylase subfamily1. This inhibitor was used in tissue culture assays to conclude that the catalytic activities of the KDM6 proteins are required in inflammatory responses1; the generation of the inhibitor is intriguing, because it provides a strategy for generating sub-type-specific inhibitors of the 27-member Jumonji family and for the future treatment of various types of disease2,3,4,5,6. Here we show that the inhibitor is not specific for the H3K27me3/me2-demethylase subfamily in vitro and in tissue culture assays. Thus, the inhibitor cannot be used alone for drawing conclusions regarding the specific role of H3K27me3/me2-demethylase activity in biological processes or disease. There is a Reply to this Brief Communications Arising by Kruidenier et al. Nature 514, http://dx.doi.org/10.1038/nature13689 (2014).
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Kruidenier, L. et al. A selective jumonji H3K27 demethylase inhibitor modulates the proinflammatory macrophage response. Nature 488, 404–408 (2012)
Helin, K. & Dhanak, D. Chromatin proteins and modifications as drug targets. Nature 502, 480–488 (2013)
Kooistra, S. M. & Helin, K. Molecular mechanisms and potential functions of histone demethylases. Nature Rev. Mol. Cell Biol. 13, 297–311. (2012)
Arrowsmith, C. H., Bountra, C., Fish, P. V., Lee, K. & Schapira, M. Epigenetic protein families: a new frontier for drug discovery. Nature Rev. Drug Discov. 11, 384–400 (2012)
Greer, E. L. & Shi, Y. Histone methylation: a dynamic mark in health, disease and inheritance. Nature Rev. Genet. 13, 343–357 (2012)
Højfeldt, J. W., Agger, K. & Helin, K. Histone lysine demethylases as targets for anticancer therapy. Nature Rev. Drug Discov. 12, 917–930 (2013)
Author information
Authors and Affiliations
Contributions
B.H., J.M.N. and H.R.H. contributed equally to this manuscript. B.H., J.M.N., H.R.H., M.J.L. and D.V.L. performed experiments and analysed data. T.B., M.L., L.-O.G., P.B. and K.H. analysed data. K.H. wrote the manuscript with input from the other authors.
Corresponding author
Ethics declarations
Competing interests
B.H., J.M.N., H.R.H., D.V.L, T.B., M.L., L.-O.G. and P.B. are employees of EpiTherapeutics Aps. K.H. is a co-founder, stockowner and consultant of EpiTherapeutics Aps. M.J.L. has no competing interests to declare.
PowerPoint slides
Rights and permissions
About this article
Cite this article
Heinemann, B., Nielsen, J., Hudlebusch, H. et al. Inhibition of demethylases by GSK-J1/J4. Nature 514, E1–E2 (2014). https://doi.org/10.1038/nature13688
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/nature13688
- Springer Nature Limited
This article is cited by
-
Comparative study of 1H-NMR metabolomic profile of canine synovial fluid in patients affected by four progressive stages of spontaneous osteoarthritis
Scientific Reports (2024)
-
Stromal nicotinamide N-methyltransferase orchestrates the crosstalk between fibroblasts and tumour cells in oral squamous cell carcinoma: evidence from patient-derived assembled organoids
Oncogene (2023)
-
Therapeutic potential of inhibiting histone 3 lysine 27 demethylases: a review of the literature
Clinical Epigenetics (2022)
-
Systematic identification of biomarker-driven drug combinations to overcome resistance
Nature Chemical Biology (2022)
-
Structural analysis of the 2-oxoglutarate binding site of the circadian rhythm linked oxygenase JMJD5
Scientific Reports (2022)