30. Dey BK, Stalker L, Schnerch A et al (2008) The histone demethylase KDM5b/JARID1b plays a
role in cell fate decisions by blocking terminal differentiation. Mol Cell Biol 28:5312–5327.
https://doi.org/10.1128/MCB.00128-08
31. Cellot S, Hope KJ, Chagraoui J et al (2013) RNAi screen identifies Jarid1b as a major regulator
of mouse HSC activity. Blood 122:1545–1555
32. Juan D, Yushi M, Ping M et al (2012) Demethylation of epiregulin gene by histone demethylase
FBXL11 and BCL6 corepressor inhibits osteo/dentinogenic differentiation. Stem Cells
31:126–136. https://doi.org/10.1002/stem.1255
33. Gao R, Dong R, Du J et al (2013) Depletion of histone demethylase KDM2A inhibited cell
proliferation of stem cells from apical papilla by de-repression of p15INK4B and p27Kip1. Mol
Cell Biochem 379:115–122. https://doi.org/10.1007/s11010-013-1633-7
34. Lu T, Jackson MW, Wang B et al (2009) Regulation of NF-κB by NSD1/FBXL11-dependent
reversible lysine methylation of p65. Response 107:1–6. https://doi.org/10.1073/pnas.
0912493107
35. Lederer D, Grisart B, Digilio MC et al (2012) Deletion of KDM6A, a histone demethylase
interacting with MLL2, in three patients with kabuki syndrome. Am J Hum Genet 90:119–124.
https://doi.org/10.1016/j.ajhg.2011.11.021
36. Noriko M, Seiji M, Nobuhiko O et al (2012) KDM6A point mutations cause kabuki syndrome.
Hum Mutat 34:108–110. https://doi.org/10.1002/humu.22229
37. Laumonnier F, Holbert S, Ronce N et al (2005) Mutations in PHF8 are associated with X linked
mental retardation and cleft lip/cleft palate. J Med Genet 42:780–786. https://doi.org/10.1136/
jmg.2004.029439
38. Gu L, Hitzel J, Moll F et al (2016) The histone demethylase PHF8 is essential for endothelial
cell migration. PLoS One 11:e0146645
39. Erdoğan Ö, Xie L, Wang L et al (2016) Proteomic dissection of LPS-inducible, PHF8dependent secretome reveals novel roles of PHF8 in TLR4-induced acute inflammation and T
cell proliferation. Sci Rep 6:24833
40. Hatch SB, Yapp C, Montenegro RC et al (2017) Assessing histone demethylase inhibitors in
cells: lessons learned. Epigenetics Chromatin 10:1–17. https://doi.org/10.1186/s13072-0170116-6
41. Vinogradova M, Gehling VS, Gustafson A et al (2016) An inhibitor of KDM5 demethylases
reduces survival of drug-tolerant cancer cells. Nat Chem Biol 12:531–538
42. Cheng Z, Cheung P, Kuo AJ et al (2014) A molecular threading mechanism underlies Jumonji
lysine demethylase KDM2A regulation of methylated H3K36. Genes Dev 28:1758–1771
43. Ng SS, Kavanagh KL, McDonough MA et al (2007) Crystal structures of histone demethylase
JMJD2A reveal basis for substrate specificity. Nature 448:87–91. https://doi.org/10.1038/
nature05971
44. Couture J-F, Collazo E, Ortiz-Tello PA et al (2007) Specificity and mechanism of JMJD2A, a
trimethyllysine-specific histone demethylase. Nat Struct Mol Biol 14:689–695. https://doi.org/
10.1038/nsmb1273
45. Chen Z, Zang J, Kappler J et al (2007) Structural basis of the recognition of a methylated histone
tail by JMJD2A. Proc Natl Acad Sci 104:10818–10823. https://doi.org/10.1073/pnas.
0704525104
46. Williams ST, Walport LJ, Hopkinson RJ et al (2015) Studies on the catalytic domains of
multiple JmjC oxygenases using peptide substrates. Epigenetics 9:1596–1603. https://doi.org/
10.4161/15592294.2014.983381
47. Chu C-H, Wang L-Y, Hsu K-C et al (2014) KDM4B as a target for prostate cancer: structural
analysis and selective inhibition by a novel inhibitor. J Med Chem 57:5975–5985. https://doi.
org/10.1021/jm500249n
48. Krishnan S, Trievel RC (2013) Structural and functional analysis of JMJD2D reveals molecular
basis for site-specific demethylation among JMJD2 demethylases. Structure 21:98–108. https://
doi.org/10.1016/j.str.2012.10.018
Inhibitors of JmjC-Containing Histone Demethylases
251
role in cell fate decisions by blocking terminal differentiation. Mol Cell Biol 28:5312–5327.
https://doi.org/10.1128/MCB.00128-08
31. Cellot S, Hope KJ, Chagraoui J et al (2013) RNAi screen identifies Jarid1b as a major regulator
of mouse HSC activity. Blood 122:1545–1555
32. Juan D, Yushi M, Ping M et al (2012) Demethylation of epiregulin gene by histone demethylase
FBXL11 and BCL6 corepressor inhibits osteo/dentinogenic differentiation. Stem Cells
31:126–136. https://doi.org/10.1002/stem.1255
33. Gao R, Dong R, Du J et al (2013) Depletion of histone demethylase KDM2A inhibited cell
proliferation of stem cells from apical papilla by de-repression of p15INK4B and p27Kip1. Mol
Cell Biochem 379:115–122. https://doi.org/10.1007/s11010-013-1633-7
34. Lu T, Jackson MW, Wang B et al (2009) Regulation of NF-κB by NSD1/FBXL11-dependent
reversible lysine methylation of p65. Response 107:1–6. https://doi.org/10.1073/pnas.
0912493107
35. Lederer D, Grisart B, Digilio MC et al (2012) Deletion of KDM6A, a histone demethylase
interacting with MLL2, in three patients with kabuki syndrome. Am J Hum Genet 90:119–124.
https://doi.org/10.1016/j.ajhg.2011.11.021
36. Noriko M, Seiji M, Nobuhiko O et al (2012) KDM6A point mutations cause kabuki syndrome.
Hum Mutat 34:108–110. https://doi.org/10.1002/humu.22229
37. Laumonnier F, Holbert S, Ronce N et al (2005) Mutations in PHF8 are associated with X linked
mental retardation and cleft lip/cleft palate. J Med Genet 42:780–786. https://doi.org/10.1136/
jmg.2004.029439
38. Gu L, Hitzel J, Moll F et al (2016) The histone demethylase PHF8 is essential for endothelial
cell migration. PLoS One 11:e0146645
39. Erdoğan Ö, Xie L, Wang L et al (2016) Proteomic dissection of LPS-inducible, PHF8dependent secretome reveals novel roles of PHF8 in TLR4-induced acute inflammation and T
cell proliferation. Sci Rep 6:24833
40. Hatch SB, Yapp C, Montenegro RC et al (2017) Assessing histone demethylase inhibitors in
cells: lessons learned. Epigenetics Chromatin 10:1–17. https://doi.org/10.1186/s13072-0170116-6
41. Vinogradova M, Gehling VS, Gustafson A et al (2016) An inhibitor of KDM5 demethylases
reduces survival of drug-tolerant cancer cells. Nat Chem Biol 12:531–538
42. Cheng Z, Cheung P, Kuo AJ et al (2014) A molecular threading mechanism underlies Jumonji
lysine demethylase KDM2A regulation of methylated H3K36. Genes Dev 28:1758–1771
43. Ng SS, Kavanagh KL, McDonough MA et al (2007) Crystal structures of histone demethylase
JMJD2A reveal basis for substrate specificity. Nature 448:87–91. https://doi.org/10.1038/
nature05971
44. Couture J-F, Collazo E, Ortiz-Tello PA et al (2007) Specificity and mechanism of JMJD2A, a
trimethyllysine-specific histone demethylase. Nat Struct Mol Biol 14:689–695. https://doi.org/
10.1038/nsmb1273
45. Chen Z, Zang J, Kappler J et al (2007) Structural basis of the recognition of a methylated histone
tail by JMJD2A. Proc Natl Acad Sci 104:10818–10823. https://doi.org/10.1073/pnas.
0704525104
46. Williams ST, Walport LJ, Hopkinson RJ et al (2015) Studies on the catalytic domains of
multiple JmjC oxygenases using peptide substrates. Epigenetics 9:1596–1603. https://doi.org/
10.4161/15592294.2014.983381
47. Chu C-H, Wang L-Y, Hsu K-C et al (2014) KDM4B as a target for prostate cancer: structural
analysis and selective inhibition by a novel inhibitor. J Med Chem 57:5975–5985. https://doi.
org/10.1021/jm500249n
48. Krishnan S, Trievel RC (2013) Structural and functional analysis of JMJD2D reveals molecular
basis for site-specific demethylation among JMJD2 demethylases. Structure 21:98–108. https://
doi.org/10.1016/j.str.2012.10.018
Inhibitors of JmjC-Containing Histone Demethylases
251