30. Wysocka J, Swigut T, Xiao H, Milne TA, Kwon SY, Landry J, Kauer M, Tackett AJ, Chait
BT, Badenhorst P, Wu C, Allis CD (2006) A PHD finger of NURF couples histone H3 lysine
4 trimethylation with chromatin remodelling. Nature 442(7098):86–90. https://doi.org/10.
1038/nature04815
31. Wang GG, Song J, Wang Z, Dormann HL, Casadio F, Li H, Luo JL, Patel DJ, Allis CD (2009)
Haematopoietic malignancies caused by dysregulation of a chromatin-binding PHD finger.
Nature 459(7248):847–851. https://doi.org/10.1038/nature08036
32. Klein BJ, Piao L, Xi Y, Rincon-Arano H, Rothbart SB, Peng D, Wen H, Larson C, Zhang X,
Zheng X, Cortazar MA, Pena PV, Mangan A, Bentley DL, Strahl BD, Groudine M, Li W,
Shi X, Kutateladze TG (2014) The histone-H3K4-specific demethylase KDM5B binds to its
substrate and product through distinct PHD fingers. Cell Rep 6(2):325–335. https://doi.org/10.
1016/j.celrep.2013.12.021
33. Dhayalan A, Tamas R, Bock I, Tattermusch A, Dimitrova E, Kudithipudi S, Ragozin S,
Jeltsch A (2011) The ATRX-ADD domain binds to H3 tail peptides and reads the combined
methylation state of K4 and K9. Hum Mol Genet 20(11):2195–2203. https://doi.org/10.1093/
hmg/ddr107
34. Iwase S, Xiang B, Ghosh S, Ren T, Lewis PW, Cochrane JC, Allis CD, Picketts DJ, Patel DJ,
Li H, Shi Y (2011) ATRX ADD domain links an atypical histone methylation recognition
mechanism to human mental-retardation syndrome. Nat Struct Mol Biol 18(7):769–776.
https://doi.org/10.1038/nsmb.2062
35. Mansfield RE, Musselman CA, Kwan AH, Oliver SS, Garske AL, Davrazou F, Denu JM,
Kutateladze TG, Mackay JP (2011) Plant homeodomain (PHD) fingers of CHD4 are histone
H3-binding modules with preference for unmodified H3K4 and methylated H3K9. J Biol
Chem 286(13):11779–11791. https://doi.org/10.1074/jbc.M110.208207
36. Musselman CA, Mansfield RE, Garske AL, Davrazou F, Kwan AH, Oliver SS, O’Leary H,
Denu JM, Mackay JP, Kutateladze TG (2009) Binding of the CHD4 PHD2 finger to histone
H3 is modulated by covalent modifications. Biochem J 423(2):179–187. https://doi.org/10.
1042/BJ20090870
37. Xi Q, Wang Z, Zaromytidou AI, Zhang XH, Chow-Tsang LF, Liu JX, Kim H, Barlas A,
Manova-Todorova K, Kaartinen V, Studer L, Mark W, Patel DJ, Massague J (2011) A poised
chromatin platform for TGF-beta access to master regulators. Cell 147(7):1511–1524. https://
doi.org/10.1016/j.cell.2011.11.032
38. Gibbons RJ, Wada T, Fisher CA, Malik N, Mitson MJ, Steensma DP, Fryer A, Goudie DR,
Krantz ID, Traeger-Synodinos J (2008) Mutations in the chromatin-associated protein ATRX.
Hum Mutat 29(6):796–802. https://doi.org/10.1002/humu.20734
39. Wang Z, Song J, Milne TA, Wang GG, Li H, Allis CD, Patel DJ (2010) Pro isomerization in
MLL1 PHD3-bromo cassette connects H3K4me readout to CyP33 and HDAC-mediated
repression. Cell 141(7):1183–1194. https://doi.org/10.1016/j.cell.2010.05.016
40. Musselman CA, Kutateladze TG (2009) PHD fingers: epigenetic effectors and potential drug
targets. Mol Interv 9(6):314–323. https://doi.org/10.1124/mi.9.6.7
41. Chi P, Allis CD, Wang GG (2010) Covalent histone modifications--miswritten, misinterpreted
and mis-erased in human cancers. Nat Rev Cancer 10(7):457–469. https://doi.org/10.1038/
nrc2876
42. van Zutven LJ, Onen E, Velthuizen SC, van Drunen E, von Bergh AR, van den Heuvel-Eibrink
MM, Veronese A, Mecucci C, Negrini M, de Greef GE, Beverloo HB (2006) Identification of
NUP98 abnormalities in acute leukemia: JARID1A (12p13) as a new partner gene. Genes
Chromosomes Cancer 45(5):437–446. https://doi.org/10.1002/gcc.20308
43. de Rooij JD, Hollink IH, Arentsen-Peters ST, van Galen JF, Berna Beverloo H, Baruchel A,
Trka J, Reinhardt D, Sonneveld E, Zimmermann M, Alonzo TA, Pieters R, Meshinchi S,
van den Heuvel-Eibrink MM, Zwaan CM (2013) NUP98/JARID1A is a novel recurrent
abnormality in pediatric acute megakaryoblastic leukemia with a distinct HOX gene expression pattern. Leukemia 27(12):2280–2288. https://doi.org/10.1038/leu.2013.87
44. Wagner EK, Nath N, Flemming R, Feltenberger JB, Denu JM (2012) Identification
and characterization of small molecule inhibitors of a plant homeodomain finger. Biochemistry
51(41):8293–8306. https://doi.org/10.1021/bi3009278
Methyl-Readers and Inhibitors
385
BT, Badenhorst P, Wu C, Allis CD (2006) A PHD finger of NURF couples histone H3 lysine
4 trimethylation with chromatin remodelling. Nature 442(7098):86–90. https://doi.org/10.
1038/nature04815
31. Wang GG, Song J, Wang Z, Dormann HL, Casadio F, Li H, Luo JL, Patel DJ, Allis CD (2009)
Haematopoietic malignancies caused by dysregulation of a chromatin-binding PHD finger.
Nature 459(7248):847–851. https://doi.org/10.1038/nature08036
32. Klein BJ, Piao L, Xi Y, Rincon-Arano H, Rothbart SB, Peng D, Wen H, Larson C, Zhang X,
Zheng X, Cortazar MA, Pena PV, Mangan A, Bentley DL, Strahl BD, Groudine M, Li W,
Shi X, Kutateladze TG (2014) The histone-H3K4-specific demethylase KDM5B binds to its
substrate and product through distinct PHD fingers. Cell Rep 6(2):325–335. https://doi.org/10.
1016/j.celrep.2013.12.021
33. Dhayalan A, Tamas R, Bock I, Tattermusch A, Dimitrova E, Kudithipudi S, Ragozin S,
Jeltsch A (2011) The ATRX-ADD domain binds to H3 tail peptides and reads the combined
methylation state of K4 and K9. Hum Mol Genet 20(11):2195–2203. https://doi.org/10.1093/
hmg/ddr107
34. Iwase S, Xiang B, Ghosh S, Ren T, Lewis PW, Cochrane JC, Allis CD, Picketts DJ, Patel DJ,
Li H, Shi Y (2011) ATRX ADD domain links an atypical histone methylation recognition
mechanism to human mental-retardation syndrome. Nat Struct Mol Biol 18(7):769–776.
https://doi.org/10.1038/nsmb.2062
35. Mansfield RE, Musselman CA, Kwan AH, Oliver SS, Garske AL, Davrazou F, Denu JM,
Kutateladze TG, Mackay JP (2011) Plant homeodomain (PHD) fingers of CHD4 are histone
H3-binding modules with preference for unmodified H3K4 and methylated H3K9. J Biol
Chem 286(13):11779–11791. https://doi.org/10.1074/jbc.M110.208207
36. Musselman CA, Mansfield RE, Garske AL, Davrazou F, Kwan AH, Oliver SS, O’Leary H,
Denu JM, Mackay JP, Kutateladze TG (2009) Binding of the CHD4 PHD2 finger to histone
H3 is modulated by covalent modifications. Biochem J 423(2):179–187. https://doi.org/10.
1042/BJ20090870
37. Xi Q, Wang Z, Zaromytidou AI, Zhang XH, Chow-Tsang LF, Liu JX, Kim H, Barlas A,
Manova-Todorova K, Kaartinen V, Studer L, Mark W, Patel DJ, Massague J (2011) A poised
chromatin platform for TGF-beta access to master regulators. Cell 147(7):1511–1524. https://
doi.org/10.1016/j.cell.2011.11.032
38. Gibbons RJ, Wada T, Fisher CA, Malik N, Mitson MJ, Steensma DP, Fryer A, Goudie DR,
Krantz ID, Traeger-Synodinos J (2008) Mutations in the chromatin-associated protein ATRX.
Hum Mutat 29(6):796–802. https://doi.org/10.1002/humu.20734
39. Wang Z, Song J, Milne TA, Wang GG, Li H, Allis CD, Patel DJ (2010) Pro isomerization in
MLL1 PHD3-bromo cassette connects H3K4me readout to CyP33 and HDAC-mediated
repression. Cell 141(7):1183–1194. https://doi.org/10.1016/j.cell.2010.05.016
40. Musselman CA, Kutateladze TG (2009) PHD fingers: epigenetic effectors and potential drug
targets. Mol Interv 9(6):314–323. https://doi.org/10.1124/mi.9.6.7
41. Chi P, Allis CD, Wang GG (2010) Covalent histone modifications--miswritten, misinterpreted
and mis-erased in human cancers. Nat Rev Cancer 10(7):457–469. https://doi.org/10.1038/
nrc2876
42. van Zutven LJ, Onen E, Velthuizen SC, van Drunen E, von Bergh AR, van den Heuvel-Eibrink
MM, Veronese A, Mecucci C, Negrini M, de Greef GE, Beverloo HB (2006) Identification of
NUP98 abnormalities in acute leukemia: JARID1A (12p13) as a new partner gene. Genes
Chromosomes Cancer 45(5):437–446. https://doi.org/10.1002/gcc.20308
43. de Rooij JD, Hollink IH, Arentsen-Peters ST, van Galen JF, Berna Beverloo H, Baruchel A,
Trka J, Reinhardt D, Sonneveld E, Zimmermann M, Alonzo TA, Pieters R, Meshinchi S,
van den Heuvel-Eibrink MM, Zwaan CM (2013) NUP98/JARID1A is a novel recurrent
abnormality in pediatric acute megakaryoblastic leukemia with a distinct HOX gene expression pattern. Leukemia 27(12):2280–2288. https://doi.org/10.1038/leu.2013.87
44. Wagner EK, Nath N, Flemming R, Feltenberger JB, Denu JM (2012) Identification
and characterization of small molecule inhibitors of a plant homeodomain finger. Biochemistry
51(41):8293–8306. https://doi.org/10.1021/bi3009278
Methyl-Readers and Inhibitors
385