histone acetyltransferase distinct from the male-specific lethal (MSL) complex. J Biol Chem
285(7):4268–4272. https://doi.org/10.1074/jbc.C109.087981
214. Thompson BA, Tremblay V, Lin G, Bochar DA (2008) CHD8 is an ATP-dependent chromatin
remodeling factor that regulates beta-catenin target genes. Mol Cell Biol 28(12):3894–3904.
https://doi.org/10.1128/MCB.00322-08
215. Chen X, Xie W, Gu P, Cai Q, Wang B, Xie Y, Dong W, He W, Zhong G, Lin T, Huang J
(2015) Upregulated WDR5 promotes proliferation, self-renewal and chemoresistance in
bladder cancer via mediating H3K4 trimethylation. Sci Rep 5:8293. https://doi.org/10.1038/
srep08293
216. Margueron R, Justin N, Ohno K, Sharpe ML, Son J, Drury 3rd WJ, Voigt P, Martin SR,
Taylor WR, De Marco V, Pirrotta V, Reinberg D, Gamblin SJ (2009) Role of the polycomb
protein EED in the propagation of repressive histone marks. Nature 461(7265):762–767.
https://doi.org/10.1038/nature08398
217. Kuzmichev A, Nishioka K, Erdjument-Bromage H, Tempst P, Reinberg D (2002) Histone
methyltransferase activity associated with a human multiprotein complex containing the
enhancer of Zeste protein. Genes Dev 16(22):2893–2905. https://doi.org/10.1101/gad.
1035902
218. Margueron R, Reinberg D (2011) The Polycomb complex PRC2 and its mark in life.
Nature 469(7330):343–349. https://doi.org/10.1038/nature09784
219. Suva ML, Riggi N, Bernstein BE (2013) Epigenetic reprogramming in cancer. Science
339(6127):1567–1570. https://doi.org/10.1126/science.1230184
220. Schuettengruber B, Bourbon HM, Di Croce L, Cavalli G (2017) Genome regulation by
polycomb and trithorax: 70 years and counting. Cell 171(1):34–57. https://doi.org/10.1016/j.
cell.2017.08.002
221. Bannister AJ, Kouzarides T (2011) Regulation of chromatin by histone modifications.
Cell Res 21(3):381–395. https://doi.org/10.1038/cr.2011.22
222. Voigt P, Tee WW, Reinberg D (2013) A double take on bivalent promoters. Genes Dev
27(12):1318–1338. https://doi.org/10.1101/gad.219626.113
223. Varambally S, Dhanasekaran SM, Zhou M, Barrette TR, Kumar-Sinha C, Sanda MG,
Ghosh D, Pienta KJ, Sewalt RG, Otte AP, Rubin MA, Chinnaiyan AM (2002) The polycomb
group protein EZH2 is involved in progression of prostate cancer. Nature 419(6907):624–629.
https://doi.org/10.1038/nature01075
224. Kleer CG, Cao Q, Varambally S, Shen R, Ota I, Tomlins SA, Ghosh D, Sewalt RG, Otte AP,
Hayes DF, Sabel MS, Livant D, Weiss SJ, Rubin MA, Chinnaiyan AM (2003) EZH2
is a marker of aggressive breast cancer and promotes neoplastic transformation of breast
epithelial cells. Proc Natl Acad Sci U S A 100(20):11606–11611. https://doi.org/10.1073/
pnas.1933744100
225. Hansen KH, Bracken AP, Pasini D, Dietrich N, Gehani SS, Monrad A, Rappsilber J,
Lerdrup M, Helin K (2008) A model for transmission of the H3K27me3 epigenetic mark.
Nat Cell Biol 10(11):1291–1300. https://doi.org/10.1038/ncb1787
226. Han Z, Xing X, Hu M, Zhang Y, Liu P, Chai J (2007) Structural basis of EZH2 recognition
by EED. Structure 15(10):1306–1315. https://doi.org/10.1016/j.str.2007.08.007
227. Patel A, Dharmarajan V, Cosgrove MS (2008) Structure of WDR5 bound to mixed lineage
leukemia protein-1 peptide. J Biol Chem 283(47):32158–32161. https://doi.org/10.1074/jbc.
C800164200
228. Patel A, Vought VE, Dharmarajan V, Cosgrove MS (2008) A conserved arginine-containing
motif crucial for the assembly and enzymatic activity of the mixed lineage leukemia protein-1
core complex. J Biol Chem 283(47):32162–32175. https://doi.org/10.1074/jbc.M806317200
229. Cao F, Townsend EC, Karatas H, Xu J, Li L, Lee S, Liu L, Chen Y, Ouillette P, Zhu J,
Hess JL, Atadja P, Lei M, Qin ZS, Malek S, Wang S, Dou Y (2014) Targeting MLL1 H3K4
methyltransferase activity in mixed-lineage leukemia. Mol Cell 53(2):247–261. https://doi.
org/10.1016/j.molcel.2013.12.001
Methyl-Readers and Inhibitors
397
285(7):4268–4272. https://doi.org/10.1074/jbc.C109.087981
214. Thompson BA, Tremblay V, Lin G, Bochar DA (2008) CHD8 is an ATP-dependent chromatin
remodeling factor that regulates beta-catenin target genes. Mol Cell Biol 28(12):3894–3904.
https://doi.org/10.1128/MCB.00322-08
215. Chen X, Xie W, Gu P, Cai Q, Wang B, Xie Y, Dong W, He W, Zhong G, Lin T, Huang J
(2015) Upregulated WDR5 promotes proliferation, self-renewal and chemoresistance in
bladder cancer via mediating H3K4 trimethylation. Sci Rep 5:8293. https://doi.org/10.1038/
srep08293
216. Margueron R, Justin N, Ohno K, Sharpe ML, Son J, Drury 3rd WJ, Voigt P, Martin SR,
Taylor WR, De Marco V, Pirrotta V, Reinberg D, Gamblin SJ (2009) Role of the polycomb
protein EED in the propagation of repressive histone marks. Nature 461(7265):762–767.
https://doi.org/10.1038/nature08398
217. Kuzmichev A, Nishioka K, Erdjument-Bromage H, Tempst P, Reinberg D (2002) Histone
methyltransferase activity associated with a human multiprotein complex containing the
enhancer of Zeste protein. Genes Dev 16(22):2893–2905. https://doi.org/10.1101/gad.
1035902
218. Margueron R, Reinberg D (2011) The Polycomb complex PRC2 and its mark in life.
Nature 469(7330):343–349. https://doi.org/10.1038/nature09784
219. Suva ML, Riggi N, Bernstein BE (2013) Epigenetic reprogramming in cancer. Science
339(6127):1567–1570. https://doi.org/10.1126/science.1230184
220. Schuettengruber B, Bourbon HM, Di Croce L, Cavalli G (2017) Genome regulation by
polycomb and trithorax: 70 years and counting. Cell 171(1):34–57. https://doi.org/10.1016/j.
cell.2017.08.002
221. Bannister AJ, Kouzarides T (2011) Regulation of chromatin by histone modifications.
Cell Res 21(3):381–395. https://doi.org/10.1038/cr.2011.22
222. Voigt P, Tee WW, Reinberg D (2013) A double take on bivalent promoters. Genes Dev
27(12):1318–1338. https://doi.org/10.1101/gad.219626.113
223. Varambally S, Dhanasekaran SM, Zhou M, Barrette TR, Kumar-Sinha C, Sanda MG,
Ghosh D, Pienta KJ, Sewalt RG, Otte AP, Rubin MA, Chinnaiyan AM (2002) The polycomb
group protein EZH2 is involved in progression of prostate cancer. Nature 419(6907):624–629.
https://doi.org/10.1038/nature01075
224. Kleer CG, Cao Q, Varambally S, Shen R, Ota I, Tomlins SA, Ghosh D, Sewalt RG, Otte AP,
Hayes DF, Sabel MS, Livant D, Weiss SJ, Rubin MA, Chinnaiyan AM (2003) EZH2
is a marker of aggressive breast cancer and promotes neoplastic transformation of breast
epithelial cells. Proc Natl Acad Sci U S A 100(20):11606–11611. https://doi.org/10.1073/
pnas.1933744100
225. Hansen KH, Bracken AP, Pasini D, Dietrich N, Gehani SS, Monrad A, Rappsilber J,
Lerdrup M, Helin K (2008) A model for transmission of the H3K27me3 epigenetic mark.
Nat Cell Biol 10(11):1291–1300. https://doi.org/10.1038/ncb1787
226. Han Z, Xing X, Hu M, Zhang Y, Liu P, Chai J (2007) Structural basis of EZH2 recognition
by EED. Structure 15(10):1306–1315. https://doi.org/10.1016/j.str.2007.08.007
227. Patel A, Dharmarajan V, Cosgrove MS (2008) Structure of WDR5 bound to mixed lineage
leukemia protein-1 peptide. J Biol Chem 283(47):32158–32161. https://doi.org/10.1074/jbc.
C800164200
228. Patel A, Vought VE, Dharmarajan V, Cosgrove MS (2008) A conserved arginine-containing
motif crucial for the assembly and enzymatic activity of the mixed lineage leukemia protein-1
core complex. J Biol Chem 283(47):32162–32175. https://doi.org/10.1074/jbc.M806317200
229. Cao F, Townsend EC, Karatas H, Xu J, Li L, Lee S, Liu L, Chen Y, Ouillette P, Zhu J,
Hess JL, Atadja P, Lei M, Qin ZS, Malek S, Wang S, Dou Y (2014) Targeting MLL1 H3K4
methyltransferase activity in mixed-lineage leukemia. Mol Cell 53(2):247–261. https://doi.
org/10.1016/j.molcel.2013.12.001
Methyl-Readers and Inhibitors
397