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  • Brief Communications Arising
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Inhibition of demethylases by GSK-J1/J4

A Brief Communications Arising to this article was published on 01 October 2014


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, (2014).

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Figure 1: GSK-J1/J4 inhibition of several histone demethylase subfamilies.

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  1. Kruidenier, L. et al. A selective jumonji H3K27 demethylase inhibitor modulates the proinflammatory macrophage response. Nature 488, 404–408 (2012)

    Article  ADS  CAS  Google Scholar 

  2. Helin, K. & Dhanak, D. Chromatin proteins and modifications as drug targets. Nature 502, 480–488 (2013)

    Article  ADS  CAS  Google Scholar 

  3. Kooistra, S. M. & Helin, K. Molecular mechanisms and potential functions of histone demethylases. Nature Rev. Mol. Cell Biol. 13, 297–311. (2012)

    Article  CAS  Google Scholar 

  4. 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)

    Article  CAS  Google Scholar 

  5. Greer, E. L. & Shi, Y. Histone methylation: a dynamic mark in health, disease and inheritance. Nature Rev. Genet. 13, 343–357 (2012)

    Article  CAS  Google Scholar 

  6. Højfeldt, J. W., Agger, K. & Helin, K. Histone lysine demethylases as targets for anticancer therapy. Nature Rev. Drug Discov. 12, 917–930 (2013)

    Article  Google Scholar 

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Authors and Affiliations



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.

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Correspondence to Kristian Helin.

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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.

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Heinemann, B., Nielsen, J., Hudlebusch, H. et al. Inhibition of demethylases by GSK-J1/J4. Nature 514, E1–E2 (2014).

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