Acknowledgement and Funding MW is supported by the EPSRC Centre for Doctoral Training
in Synthesis for Biology and Medicine (EP/L015838/1). AK gratefully acknowledges the Royal
Society for the Dorothy Hodgkin Fellowship, the European Research Council Starting Grant
(EPITOOLS-679479) and Cancer Research UK Programme Grant (C8717/A18245). The SGC is
a registered charity (number 1097737) that receives funds from AbbVie, Bayer Pharma AG,
Boehringer Ingelheim, Canada Foundation for Innovation, Eshelman Institute for Innovation,
Genome Canada, Innovative Medicines Initiative (EU/EFPIA) [ULTRA-DD grant no. 115766],
Janssen, Merck KGaA Darmstadt Germany, MSD, Novartis Pharma AG, Ontario Ministry of
Economic Development and Innovation, Pfizer, São Paulo Research Foundation-FAPESP, Takeda
and Wellcome [106169/ZZ14/Z]. The authors acknowledge the EU COST Action CM1406. We
apologise for the incomplete citations and for the research that we were not able to cite due to space
constraints.
Compliance and Ethical Standards
Conflict of Interest: The authors declare that they have no conflict of interest.
Ethical approval: This article does not contain any studies with human participants or animals
performed by any of the authors.
References
1. Klose RJ, Zhang Y (2007) Regulation of histone methylation by demethylimination and
demethylation. Nat Rev Mol Cell Biol 8:307–318. https://doi.org/10.1038/nrm2143
2. Højfeldt JW (2013) Histone lysine demethylases as targets for anticancer therapy. Nat Rev Drug
Discov 12:917–930. https://doi.org/10.1038/nrd4154
3. Cloos PAC, Christensen J, Agger K, Helin K (2008) Erasing the methyl mark: histone
demethylases at the center of cellular differentiation and disease. Genes Dev 22:1115–1140.
https://doi.org/10.1101/gad.1652908
4. Markolovic S, Leissing TM, Chowdhury R et al (2016) Structure – function relationships of
human JmjC oxygenases – demethylases versus hydroxylases. Curr Opin Struct Biol 41:62–72.
https://doi.org/10.1016/j.sbi.2016.05.013
5. Lu T, Jackson MW, Wang B et al (2010) Regulation of NF-kappaB by NSD1/FBXL11dependent reversible lysine methylation of p65. Proc Natl Acad Sci U S A 107:46–51.
https://doi.org/10.1073/pnas.0912493107
6. Solá S, Xavier JM, Santos DM et al (2011) p53 interaction with JMJD3 results in its nuclear
distribution during mouse neural stem cell differentiation. PLoS One 6:e18421. https://doi.org/
10.1371/journal.pone.0018421
7. Walport L, Hopkinson R, Chowdhury R et al (2016) Arginine demethylation is catalysed by a
subset of JmjC histone lysine demethylases. Nat Commun 7:11974. https://doi.org/10.1038/
ncomms11974
8. Horton JR, Upadhyay AK, Qi HH et al (2010) Enzymatic and structural insights for substrate
specificity of a family of Jumonji histone lysine demethylases. Nat Struct Mol Biol 17:38–43.
https://doi.org/10.1038/nsmb.1753
9. Torres IO, Kuchenbecker KM, Nnadi CI et al (2015) Histone demethylase KDM5A is regulated
by its reader domain through a positive-feedback mechanism. Nat Commun 6:6204. https://doi.
org/10.1038/ncomms7204
10. Landeira D, Fisher AG (2011) Inactive yet indispensable: the tale of Jarid2. Trends Cell Biol
21:74–80. https://doi.org/10.1016/j.tcb.2010.10.004
Inhibitors of JmjC-Containing Histone Demethylases
249
in Synthesis for Biology and Medicine (EP/L015838/1). AK gratefully acknowledges the Royal
Society for the Dorothy Hodgkin Fellowship, the European Research Council Starting Grant
(EPITOOLS-679479) and Cancer Research UK Programme Grant (C8717/A18245). The SGC is
a registered charity (number 1097737) that receives funds from AbbVie, Bayer Pharma AG,
Boehringer Ingelheim, Canada Foundation for Innovation, Eshelman Institute for Innovation,
Genome Canada, Innovative Medicines Initiative (EU/EFPIA) [ULTRA-DD grant no. 115766],
Janssen, Merck KGaA Darmstadt Germany, MSD, Novartis Pharma AG, Ontario Ministry of
Economic Development and Innovation, Pfizer, São Paulo Research Foundation-FAPESP, Takeda
and Wellcome [106169/ZZ14/Z]. The authors acknowledge the EU COST Action CM1406. We
apologise for the incomplete citations and for the research that we were not able to cite due to space
constraints.
Compliance and Ethical Standards
Conflict of Interest: The authors declare that they have no conflict of interest.
Ethical approval: This article does not contain any studies with human participants or animals
performed by any of the authors.
References
1. Klose RJ, Zhang Y (2007) Regulation of histone methylation by demethylimination and
demethylation. Nat Rev Mol Cell Biol 8:307–318. https://doi.org/10.1038/nrm2143
2. Højfeldt JW (2013) Histone lysine demethylases as targets for anticancer therapy. Nat Rev Drug
Discov 12:917–930. https://doi.org/10.1038/nrd4154
3. Cloos PAC, Christensen J, Agger K, Helin K (2008) Erasing the methyl mark: histone
demethylases at the center of cellular differentiation and disease. Genes Dev 22:1115–1140.
https://doi.org/10.1101/gad.1652908
4. Markolovic S, Leissing TM, Chowdhury R et al (2016) Structure – function relationships of
human JmjC oxygenases – demethylases versus hydroxylases. Curr Opin Struct Biol 41:62–72.
https://doi.org/10.1016/j.sbi.2016.05.013
5. Lu T, Jackson MW, Wang B et al (2010) Regulation of NF-kappaB by NSD1/FBXL11dependent reversible lysine methylation of p65. Proc Natl Acad Sci U S A 107:46–51.
https://doi.org/10.1073/pnas.0912493107
6. Solá S, Xavier JM, Santos DM et al (2011) p53 interaction with JMJD3 results in its nuclear
distribution during mouse neural stem cell differentiation. PLoS One 6:e18421. https://doi.org/
10.1371/journal.pone.0018421
7. Walport L, Hopkinson R, Chowdhury R et al (2016) Arginine demethylation is catalysed by a
subset of JmjC histone lysine demethylases. Nat Commun 7:11974. https://doi.org/10.1038/
ncomms11974
8. Horton JR, Upadhyay AK, Qi HH et al (2010) Enzymatic and structural insights for substrate
specificity of a family of Jumonji histone lysine demethylases. Nat Struct Mol Biol 17:38–43.
https://doi.org/10.1038/nsmb.1753
9. Torres IO, Kuchenbecker KM, Nnadi CI et al (2015) Histone demethylase KDM5A is regulated
by its reader domain through a positive-feedback mechanism. Nat Commun 6:6204. https://doi.
org/10.1038/ncomms7204
10. Landeira D, Fisher AG (2011) Inactive yet indispensable: the tale of Jarid2. Trends Cell Biol
21:74–80. https://doi.org/10.1016/j.tcb.2010.10.004
Inhibitors of JmjC-Containing Histone Demethylases
249