152. Wagner T, Greschik H, Burgahn T, Schmidtkunz K, Schott AK, McMillan J, Baranauskiene L,
Xiong Y, Fedorov O, Jin J, Oppermann U, Matulis D, Schule R, Jung M (2016) Identification
of a small-molecule ligand of the epigenetic reader protein Spindlin1 via a versatile screening
platform. Nucleic Acids Res 44(9):e88. https://doi.org/10.1093/nar/gkw089
153. Sweis RF, Pliushchev M, Brown PJ, Guo J, Li F, Maag D, Petros AM, Soni NB, Tse C,
Vedadi M, Michaelides MR, Chiang GG, Pappano WN (2014) Discovery and development
of potent and selective inhibitors of histone methyltransferase g9a. ACS Med Chem Lett
5(2):205–209. https://doi.org/10.1021/ml400496h
154. Robaa D, Wagner T, Luise C, Carlino L, McMillan J, Flaig R, Schule R, Jung M, Sippl W
(2016) Identification and structure-activity relationship studies of small-molecule inhibitors of
the methyllysine reader protein Spindlin1. ChemMedChem 11(20):2327–2338. https://doi.
org/10.1002/cmdc.201600362
155. Bae N, Gao M, Li X, Premkumar T, Sbardella G, Chen J, Bedford MT (2017) A transcriptional
coregulator, SPIN.DOC, attenuates the coactivator activity of Spindlin1. J Biol Chem
292(51):20808–20817. https://doi.org/10.1074/jbc.M117.814913
156. Berry WL, Janknecht R (2013) KDM4/JMJD2 histone demethylases: epigenetic regulators
in cancer cells. Cancer Res 73(10):2936–2942. https://doi.org/10.1158/0008-5472.CAN-124300
157. Singh RN, Howell MD, Ottesen EW, Singh NN (2017) Diverse role of survival motor neuron
protein. Biochim Biophys Acta Gene Regul Mech 1860(3):299–315. https://doi.org/10.1016/j.
bbagrm.2016.12.008
158. Yang Y, McBride KM, Hensley S, Lu Y, Chedin F, Bedford MT (2014) Arginine methylation
facilitates the recruitment of TOP3B to chromatin to prevent R loop accumulation. Mol Cell
53(3):484–497. https://doi.org/10.1016/j.molcel.2014.01.011
159. Zheng S, Moehlenbrink J, Lu YC, Zalmas LP, Sagum CA, Carr S, McGouran JF, Alexander L,
Fedorov O, Munro S, Kessler B, Bedford MT, Yu Q, La Thangue NB (2013) Arginine
methylation-dependent reader-writer interplay governs growth control by E2F-1. Mol Cell
52(1):37–51. https://doi.org/10.1016/j.molcel.2013.08.039
160. Vagin VV, Wohlschlegel J, Qu J, Jonsson Z, Huang X, Chuma S, Girard A, Sachidanandam R,
Hannon GJ, Aravin AA (2009) Proteomic analysis of murine Piwi proteins reveals a role
for arginine methylation in specifying interaction with Tudor family members. Genes Dev
23(15):1749–1762. https://doi.org/10.1101/gad.1814809
161. Bonasio R, Lecona E, Reinberg D (2010) MBT domain proteins in development and disease.
Semin Cell Dev Biol 21(2):221–230. https://doi.org/10.1016/j.semcdb.2009.09.010
162. Lewis PW, Beall EL, Fleischer TC, Georlette D, Link AJ, Botchan MR (2004)
Identification of a Drosophila Myb-E2F2/RBF transcriptional repressor complex. Genes Dev
18(23):2929–2940. https://doi.org/10.1101/gad.1255204
163. Wang WK, Tereshko V, Boccuni P, MacGrogan D, Nimer SD, Patel DJ (2003) Malignant
brain tumor repeats: a three-leaved propeller architecture with ligand/peptide binding pockets.
Structure 11(7):775–789. https://doi.org/10.1016/S0969-2126(03)00127-8
164. Sathyamurthy A, Allen MD, Murzin AG, Bycroft M (2003) Crystal structure of the malignant
brain tumor (MBT) repeats in Sex Comb on Midleg-like 2 (SCML2). J Biol Chem 278
(47):46968–46973. https://doi.org/10.1074/jbc.M306469200
165. Nady N, Krichevsky L, Zhong N, Duan S, Tempel W, Amaya MF, Ravichandran M,
Arrowsmith CH (2012) Histone recognition by human malignant brain tumor domains.
J Mol Biol 423(5):702–718. https://doi.org/10.1016/j.jmb.2012.08.022
166. Min J, Allali-Hassani A, Nady N, Qi C, Ouyang H, Liu Y, MacKenzie F, Vedadi M,
Arrowsmith CH (2007) L3MBTL1 recognition of mono- and dimethylated histones.
Nat Struct Mol Biol 14(12):1229–1230. https://doi.org/10.1038/nsmb1340
167. Eryilmaz J, Pan P, Amaya MF, Allali-Hassani A, Dong A, Adams-Cioaba MA, Mackenzie F,
Vedadi M, Min J (2009) Structural studies of a four-MBT repeat protein MBTD1. PLoS One
4(10):e7274. https://doi.org/10.1371/journal.pone.0007274
Methyl-Readers and Inhibitors
393
Xiong Y, Fedorov O, Jin J, Oppermann U, Matulis D, Schule R, Jung M (2016) Identification
of a small-molecule ligand of the epigenetic reader protein Spindlin1 via a versatile screening
platform. Nucleic Acids Res 44(9):e88. https://doi.org/10.1093/nar/gkw089
153. Sweis RF, Pliushchev M, Brown PJ, Guo J, Li F, Maag D, Petros AM, Soni NB, Tse C,
Vedadi M, Michaelides MR, Chiang GG, Pappano WN (2014) Discovery and development
of potent and selective inhibitors of histone methyltransferase g9a. ACS Med Chem Lett
5(2):205–209. https://doi.org/10.1021/ml400496h
154. Robaa D, Wagner T, Luise C, Carlino L, McMillan J, Flaig R, Schule R, Jung M, Sippl W
(2016) Identification and structure-activity relationship studies of small-molecule inhibitors of
the methyllysine reader protein Spindlin1. ChemMedChem 11(20):2327–2338. https://doi.
org/10.1002/cmdc.201600362
155. Bae N, Gao M, Li X, Premkumar T, Sbardella G, Chen J, Bedford MT (2017) A transcriptional
coregulator, SPIN.DOC, attenuates the coactivator activity of Spindlin1. J Biol Chem
292(51):20808–20817. https://doi.org/10.1074/jbc.M117.814913
156. Berry WL, Janknecht R (2013) KDM4/JMJD2 histone demethylases: epigenetic regulators
in cancer cells. Cancer Res 73(10):2936–2942. https://doi.org/10.1158/0008-5472.CAN-124300
157. Singh RN, Howell MD, Ottesen EW, Singh NN (2017) Diverse role of survival motor neuron
protein. Biochim Biophys Acta Gene Regul Mech 1860(3):299–315. https://doi.org/10.1016/j.
bbagrm.2016.12.008
158. Yang Y, McBride KM, Hensley S, Lu Y, Chedin F, Bedford MT (2014) Arginine methylation
facilitates the recruitment of TOP3B to chromatin to prevent R loop accumulation. Mol Cell
53(3):484–497. https://doi.org/10.1016/j.molcel.2014.01.011
159. Zheng S, Moehlenbrink J, Lu YC, Zalmas LP, Sagum CA, Carr S, McGouran JF, Alexander L,
Fedorov O, Munro S, Kessler B, Bedford MT, Yu Q, La Thangue NB (2013) Arginine
methylation-dependent reader-writer interplay governs growth control by E2F-1. Mol Cell
52(1):37–51. https://doi.org/10.1016/j.molcel.2013.08.039
160. Vagin VV, Wohlschlegel J, Qu J, Jonsson Z, Huang X, Chuma S, Girard A, Sachidanandam R,
Hannon GJ, Aravin AA (2009) Proteomic analysis of murine Piwi proteins reveals a role
for arginine methylation in specifying interaction with Tudor family members. Genes Dev
23(15):1749–1762. https://doi.org/10.1101/gad.1814809
161. Bonasio R, Lecona E, Reinberg D (2010) MBT domain proteins in development and disease.
Semin Cell Dev Biol 21(2):221–230. https://doi.org/10.1016/j.semcdb.2009.09.010
162. Lewis PW, Beall EL, Fleischer TC, Georlette D, Link AJ, Botchan MR (2004)
Identification of a Drosophila Myb-E2F2/RBF transcriptional repressor complex. Genes Dev
18(23):2929–2940. https://doi.org/10.1101/gad.1255204
163. Wang WK, Tereshko V, Boccuni P, MacGrogan D, Nimer SD, Patel DJ (2003) Malignant
brain tumor repeats: a three-leaved propeller architecture with ligand/peptide binding pockets.
Structure 11(7):775–789. https://doi.org/10.1016/S0969-2126(03)00127-8
164. Sathyamurthy A, Allen MD, Murzin AG, Bycroft M (2003) Crystal structure of the malignant
brain tumor (MBT) repeats in Sex Comb on Midleg-like 2 (SCML2). J Biol Chem 278
(47):46968–46973. https://doi.org/10.1074/jbc.M306469200
165. Nady N, Krichevsky L, Zhong N, Duan S, Tempel W, Amaya MF, Ravichandran M,
Arrowsmith CH (2012) Histone recognition by human malignant brain tumor domains.
J Mol Biol 423(5):702–718. https://doi.org/10.1016/j.jmb.2012.08.022
166. Min J, Allali-Hassani A, Nady N, Qi C, Ouyang H, Liu Y, MacKenzie F, Vedadi M,
Arrowsmith CH (2007) L3MBTL1 recognition of mono- and dimethylated histones.
Nat Struct Mol Biol 14(12):1229–1230. https://doi.org/10.1038/nsmb1340
167. Eryilmaz J, Pan P, Amaya MF, Allali-Hassani A, Dong A, Adams-Cioaba MA, Mackenzie F,
Vedadi M, Min J (2009) Structural studies of a four-MBT repeat protein MBTD1. PLoS One
4(10):e7274. https://doi.org/10.1371/journal.pone.0007274
Methyl-Readers and Inhibitors
393