SUPPLEMENTARY INFORMATIONIn format provided by Biggar & Li(January 2015)
Supplementary information S1 (table) |
Non-histone Lys methylation
PROTEIN / UNIPROT ID / RESIDUE / STATE / KMT / REFERENCESCellular process:
TRANSCRIPTION
p53 / P04637 / 370 / 1Me / SMYD2 / 1,2
372 / 1Me / SETD7 / 1,3-7
373 / 2Me / GLP / 8, 9
382 / 1Me / SETD8 / 10
RB / P06400 / 810/873 / 1Me / SETD7 / 11,12
810/860 / 1Me / SMYD2 / 13,14
E2F1 / Q01094 / 185 / 1Me / SETD7 / 15-18
RELA / Q04206 / 37/314/315 / 1Me / SETD7 / 19,20
218/221 / 1Me/2Me / NSD1 / 21
310 / 1Me / SETD6 / 22
TAF7 / Q15545 / 5 / 1Me / SETD7 / 23
TAF10 / Q12962 / 189 / 1Me / SETD7 / 24
YAP / P46938 / 494 / 1Me / SETD7 / 25
STAT3 / P40763 / 140 / 2Me / SETD7 / 26
180 / ? / EZH2 / 27
FOXO3 / O43524 / 270/271 / 1Me / SETD7 / 28,29
MYPT1 / O14974 / 442 / 1Me / SETD7 / 30
MEF2D / Q63943 / 267 / 1/2Me / G9a / 31
GATA4 / P43694 / 299 / 1Me / EZH2 / 32
MTA1 / Q13330 / 532 / 2Me / G9a / 33
RUVBL2 / Q9Y230 / 67 / 1Me / G9a / 34
C/EBP / Q05826 / 39 / ? / G9a / 35
MYOD / P15172 / 104 / 1Me/2Me / G9a / 36
WIZ / O95785 / 305 / 3Me / G9a / 37
IRF1/2 / P10914 / 126/134 / 1Me/2Me / SETD7 / 38
PIAS2 / Q96T58 / 2076 / 2Me / SETD7 / 38
PDX1 / P52945 / ? / ? / SETD7 / 39
ER / P03372 / 302 / 1Me / SETD7 / 40
266 / SMYD2 / 41
AR / P10275 / 630/632 / 1Me / SETD7 / 42,43
RORα / P51448 / 38 / 1Me / EZH2 / 44
FXR / P51114 / 206 / ? / SETD7 / 45
KLF12 / Q9Y4X4 / 313 / 1Me / G9a / 46
GFI-1B / Q5VTD9 / 8 / 2Me / SETD7 / 47
CHROMATIN/CHROMOSOMAL REGULATION
EED / O75530 / 66/197/268/284 / 2Me / G9a / 48
CENPC / Q03188 / 414 / 1Me / SETD7 / 49
MECP2 / P51608 / 347 / 1Me / SETD7 / 49
DNA REPLICATION, SYNTHESIS & REPAIR
PCNA / P12004 / 248 / 1Me / SETD8 / 50
PARP1 / P09874 / 508 / 1Me / SETD7 / 51
CSB / Q03468 / G9a / 37
KIN17 / O60870 / 135 / 3Me / METTL22 / 52
PROTEIN SYNTHESIS
PPARBP / Q15648 / 1006 / ? / SETD7 / 49
METHYLTRANSFERASES/DEMETHYLASES
DNMT1 / P26358, P13864 / 70 / 2Me / G9a / 37
142/1094 / 1Me / SETD7 / 53,54
DNMT3a / Q9Y6K1, O88508 / 44 / 2Me / G9a, GLP / 55
SUV39H1 / O43463 / 105/123 / 1Me / SETD7 / 56
G9a / Q96KQ7 / 165 / 2/3Me / G9a / 57
239 / 3Me / G9a / 57
GLP / Q9H9B1 / 174 / ? / G9a / 58
205 / ? / GLP / 58
MAM / Q6VMQ6 / 16 / ? / G9a / 58
METTL21A / Q8WXB1 / ? / ? / METTL21A / 59
CAKMT / Q7Z624 / ? / ? / CaKMT / 60
ACETYLTRANSFERASES/DEACETYLASES
PCAF / Q92831 / 78/89 / 1Me / SETD7 / 61
CDYL1 / Q9Y232 / 135 / 3Me / G9a / 62
SIRT1 / Q96EB6 / 233, 235, 236, 238 / 1Me? / SETD7 / 63
HDAC1 / Q13547 / 432 / ? / G9a / 46
KINASES/PHOSPHATASES
TTK / P33981 / 708/710? / ? / SETD7 / 49
PAK4 / O96013 / ? / 1/3Me? / SETD6 / 64
PLK1 / P53350 / ? / 1/3Me? / SETD6 / 64
CHAPERONES
HSP90 / P07900 / 209/615 / 1Me / SMYD2 / 65
HSP70 / P08107 / 561 / 2Me / SETD1A / 66
DNAJC8 / O75937 / ? / ? / SETD6 / 64
METABOLISM
CAMK / P62158 / 115 / 3Me / CaKMT / 67
PROTEASES, PROTEASOME
ACINUS / Q9UKV3 / 654 / 3Me / G9a / 46
CULLIN1 / Q13616 / 73 / ? / SETD7 / 49
VIRAL PROTEINS
TAT / P04610 / 50/51 / 3Me? / SETDB1 / 68
51 / 1Me / SETD7 / 69
MEMBRANE PROTEINS
NUMB / P49757 / 158/163 / 2Me / SETD8 / 70
ZDHHC8 / Q9ULC8 / 300 / 1Me / SETD7 / 49
AKAP6 / Q13023 / 604 / ? / SETD7 / 49
CELLULAR SIGNALING
MAP3K2 / Q9Y2U5 / 260 / 1/2/3Me / SMYD3 / 71
VEGFR / P17948 / 831 / 2Me / SMYD3 / 72
Non-histone Arg methylation
PROTEIN / UNIPROT ID / RESIDUE / PRMT / REFERENCECellular process:
TRANSCRIPTION
RUNX1 / Q01196 / No specific site defined / PRMT4 / 73
206/210 / PRMT1 / 74
E2F1 / Q61501 / 109 / PRMT1 / 75
111/113 / PRMT5 / 76
TRF2 / P62380 / 17 / PRMT1 / 77
TLS2 / P35637 / NS / PRMT1 / 78
ILF3 / Q12906 / COOH-terminal region / PRMT1 / 79
ER / P11474 / 260 / PRMT1 / 80
AF-1 (DNA binding domain and hormone binding domain) / PRMT2 / 81
TAF15 / Q92804 / RGG repeats / PRMT1 / 82
P300 / Q09472 / 2142 / PRMT4 / 83
SOX9 / P48436 / high-mobility group (HMG) domain / PRMT4 / 84
TAF2S / O14776 / proline-, glycine-, methionine-rich (PGM) / PRMT4 / 85
p53 / P04637 / 333/335/337 / PRMT5 / 86
HOXA / P49639 / 140 / PRMT5 / 87
RELA / Q2TAM5 / 30 / PRMT5 / 88
CHROMATIN/CHROMOSOMAL REGULATION
SMARCC1 / Q92922 / 1064 / PRMT4 / 89
HMGA1 / Q6IPL9 / 57/59 / PRMT6 / 90
DNA REPLICATION, SYNTHESIS & REPAIR
53BP1 / Q12888 / GAR / PRMT1 / 91
MRE11 / P49959 / GAR / PRMT1 / 92
POLL / Q9UGP5 / 83/152 / PRMT6 / 93
PROTEIN SYNTHESIS
PABP1 / P11940 / 455/460 / PRMT4 / 94
METHYLTRANSFERASES/DEMETHYLASES
ASH2L / Q9UBL3 / 296 / PRMT1 / 95
296 / PRMT5 / 95
CHAPERONES
SERPINH1 / P50454 / 234 / PRMT5 / 96
METABOLISM
PFKFB3 / Q16875 / 131/134 / PRMT1 / 97
GST / P12653 / GAR / PRMT2 / 98
VIRAL PROTEINS
TAT / P04610 / 49-63 / PRMT6 / 99
CELLULAR SIGNALING
BTG1 / P62324 / No specific site defined / PRMT1 / 100
IFN α/β / P17181 / Intracytoplasmic domain (IC) / PRMT1 / 101
BCR / P11274 / 198 / PRMT1 / 102
APOPTOSIS
PDCD4 / Q53EL6 / 110 / PRMT5 / 103
CYTOSKELETAL RELATED
MBP / P02686 / 107 / PRMT5 / 104
No specific site defined / PRMT8 / 105
RNA BINDING, PROCESSING
CPSF6 / Q16630 / GAR / PRMT1 / 106
GAR / PRMT5 / 106
CPSF7 / Q8N684 / GAR / PRMT1 / 106
HNRNP A1 / P09651 / 194 / PRMT1 / 107
SPT5 / O00267 / 681/696/698 / PRMT1 / 108
HNRNPU / Q00839 / 778-793 / PRMT1 / 109
FMRP / Q06787 / 544/546 / PRMT1/3/4 / 110
KHDRBS1 / Q07666 / 280-339 / PRMT1 / 111
SLM / Q5VWX1 / GAR / PRMT1 / 111
RPS2 / Q9BSW5 / GAR / PRMT3 / 112
SNRPB / P14678 / PGM / PRMT4 / 85
SNRPC / P09234 / PGM / PRMT4 / 85
SF3B4 / Q15427 / PGM / PRMT4 / 85
LSM4 / Q9Y4Z0 / No specific site defined / PRMT5 / 113
SNRPD1 / P62314 / GAR / PRMT5 / 113
SNRPD3 / P62318 / GAR / PRMT5 / 113
EBNA1 / Q1HVF7 / 325-376 / PRMT5 / 114
EBNA2 / P12978 / 325-376 / PRMT5 / 115
SPT5 / O00267 / 698 / PRMT5 / 116
EWSR1 / Q01844 / Arginine-glycine-glycine repeats (RGG) / PRMT8 / 117
References
1. Huang, J. et al. p53 is regulated by the lysine demethylase LSD1.Nature449(7158), 105-108 (2007)
2. Cui, G. et al. PHF20 is an effector protein of p53 double lysine methylation that stabilizes and activates p53.Nat. Struct. Mol. Biol.19, 916-24 (2012).
3. Chuikov, S.et al. Regulation of p53 activity through lysine methylation.Nature432, 353-360 (2004).
4. Ivanov,G.S. et al. Methylation-acetylation interplay activates p53 in response to DNA damage.Mol. Cell.Biol.27, 6756-69 (2007).
5. Hsu, C.H. et al. The HPV E6 oncoprotein targets histone methyltransferases for modulating specific gene transcription. Oncogene31, 2335-2349 (2012).
6. Campaner,S. et al. The methyltransferase Set7/9 (Setd7) is dispensable for the p53-mediated DNA damage response in vivo.Mol. Cell43, 681-8 (2011).
7. Lehnertz,B.et al. p53-dependent transcription and tumor suppression are not affected in Set7/9-deficient mice.Mol. Cell43, 673-80 (2011).
8. Huang,J. et al. G9a and Glp methylate lysine 373 in the tumor suppressor p53.J. Biol. Chem. 285, 9636-41 (2010).
9. Chen, L. et al. MDM2 recruitment of lysine methyltransferases regulates p53 transcriptional output. EMBO J.29, 2538-3552 (2010).
10. Shi,X. et al. Modulation ofp53function by SET8-mediatedmethylationat lysine 382.Mol. Cell27, 636-46 (2007).
11. Carr, S.M. et al.Interplay between lysine methylation and Cdk phosphorylation in growth control by the retinoblastoma protein.EMBO J.30, 317-27 (2011).
12. Munro, S. et al.Lysine methylation regulates the pRb tumour suppressor protein.Oncogene29, 2357-67 (2010).
13. Cho, Y.et al. chemoprotective fish oil/pectin diet enhances apoptosis via Bcl-2 promoter methylation in rat azoxymethane-induced carcinomas.Exp. Biol. Med (Maywood).237, 1387-93 (2012).
14.Saddic, L.A. et al. Methylation of the retinoblastoma tumor suppressor by SMYD2.J. Biol. Chem. 285, 37733-40 (2010).
15.Kontaki, H. & Talianidis, I.Lysine methylation regulates E2F1-induced cell death. Mol. Cell39, 152-60 (2010).
16. Loftus, S.J., Liu, G., Carr, S.M., Munro, S. & La Thangue, N.B.NEDDylation regulates E2F-1-dependent transcription.EMBO Rep. 13, 811-8 (2012).
17.Montenegro, M.F., Sáez-Ayala, M., Piñero-Madrona, A., Cabezas-Herrera, J. & Rodríguez-López, J.N.Reactivation of the tumour suppressor RASSF1A in breast cancer by simultaneous targeting of DNA and E2F1 methylation.PLoS One7, e52231 (2012).
18.Xie, Q. et al.Methylation-mediated regulation of E2F1 in DNA damage-induced cell death.J. Recept. signal Transduct. Res. 31, 139-46 (2011).
19.Ea, C.K. & Baltimore, D.Regulation of NF-kappaB activity through lysine monomethylation of p65.Proc. Natl. Acad. Sci. USA106, 18972-7 (2009).
20.Yang, X.D. et al.Negative regulation of NF-kappaB action by Set9-mediated lysine methylation of the RelA subunit. EMBO J.28, 1055-66 (2009).
21.Lu, T. et al.Regulation of NF-kappaB by NSD1/FBXL11-dependent reversible lysine methylation of p65.Proc. Natl. Acad. Sci. USA107, 46-51 (2010).
22.Levy, D. et al.Lysine methylation of the NF-κB subunit RelA by SETD6 couples activity of the histone methyltransferase GLP at chromatin to tonic repression of NF-κB signaling.Nat. Immunol. 12, 29-36 (2011).
23.Couture, J.F., Collazo, E., Hauk, G. & Trievel, R.C.Structural basis for the methylation site specificity of SET7/9.Nat. Struct. Mol. Biol.13, 140-6 (2006).
24. Kouskouti, A., Scheer, E., Staub, A., Tora, L. & Talianidis, I.Gene-specific modulation of TAF10 function by SET9-mediated methylation.Mol. Cell14, 175-82 (2004).
25.Oudhoff, M.J. et al.Control of the hippo pathway by Set7-dependent methylation of Yap.Dev. Cell26, 188-94 (2013).
26.Yang, J. et al.Reversible methylation of promoter-bound STAT3 by histone-modifying enzymes.Proc. Natl. Acad. Sci. USA107, 21499-504 (2010).
27.Kim, E. et al.Phosphorylation of EZH2 activates STAT3 signaling via STAT3 methylation and promotes tumorigenicity of glioblastoma stem-like cells.Cancer Cell. 23, 839-52 (2010).
28.Xie, Q. et al.Lysine methylation of FOXO3 regulates oxidative stress-induced neuronal cell death. EMBO Rep. 13, 371-7 (2012).
29.Calnan, D.R. et al.Methylation by Set9 modulates FoxO3 stability and transcriptional activity.Aging (Albany NY). 4, 462-79 (2012).
30.Cho, H.S. et al. Demethylation of RB regulator MYPT1 by histone demethylase LSD1 promotes cell cycle progression in cancer cells.Cancer Res.71, 655-60 (2011).
31.Choi, S.Y. et al.Phosphorylation and ubiquitination-dependent degradation of CABIN1 releases p53 for transactivation upon genotoxic stress.Nucleic Acids Res. 41, 2180-90 (2013).
32.He, A. et al.PRC2 directly methylates GATA4 and represses its transcriptional activity. Genes Dev. 26, 37-42 (2012).
33.Nair, S.S., Li, D.Q. & Kumar, R.A core chromatin remodeling factor instructs global chromatin signaling through multivalent reading of nucleosome codes.Mol. Cell49, 704-18 (2013).
34.Lee, J.S. et al. Negative regulation of hypoxic responses via induced Reptin methylation.Mol. Cell39, 71-85 (2010).
35. Pless, O. et al.G9a-mediated lysine methylation alters the function of CCAAT/enhancer-binding protein-beta.J. Biol. Chem. 283, 26357-63 (2008).
36. Ling, B.M. et al.Lysine methyltransferase G9a methylates the transcription factor MyoD and regulates skeletal muscle differentiation.Proc. Natl. Acad. Sci. USA109, 841-6 (2012).
37. Rathert, P. et al.Protein lysine methyltransferase G9a acts on non-histone targets.Nat. Chem. Biol. 4, 344-6 (2008).
38. Dhayalan, A., Kudithipudi, S., Rathert, P. & Jeltsch, A.Specificity analysis-based identification of new methylation targets of the SET7/9 protein lysine methyltransferase.Chem. Biol.18, 111-20 (2011).
39. Francis, J., Chakrabarti, S.K., Garmey, J.C. & Mirmira, R.G.Pdx-1 links histone H3-Lys-4 methylation to RNA polymerase II elongation during activation of insulin transcription.J. Biol. Chem. 280, 36244-53 (2005).
40. Subramanian, K. et al.Regulation of estrogen receptor alpha by the SET7 lysine methyltransferase.Mol. Cell30, 336-47 (2008).
41. Zhang, X. et al.Regulation of estrogen receptor α by histone methyltransferase SMYD2-mediated protein methylation.Proc. Natl. Acad. Sci. USA110, 17284-9 (2013).
42. Ko, S. et al.Lysine methylation and functional modulation of androgen receptor by Set9 methyltransferase.Mol. Endocrinol. 25, 433-44 (2011).
43. Gaughan, L. et al.Regulation of the androgen receptor by SET9-mediated methylation.Nucleic Acids Res.39, 1266-79 (2011).
44. Lee, J.M. et al.EZH2 generates a methyl degron that is recognized by the DCAF1/DDB1/CUL4 E3 ubiquitin ligase complex.Mol. Cell48, 572-86 (2012).
45. Balasubramaniyan, N., Ananthanarayanan, M. & Suchy, F.J.Direct methylation of FXR by Set7/9, a lysine methyltransferase, regulates the expression of FXR target genes.Am. J. Physiol. Gastrointest. Liver Physiol.302, G937-47 (2012).
46. Rathert, P. et al.Protein lysine methyltransferase G9a acts on non-histone targets.Nat. Chem. Biol. 4, 344-6 (2008).
47. Laurent, L. et al.Dynamic changes in the human methylome during differentiation.Genome Res.20, 320-31 (2010).
48. Xu, C. et al.Binding of different histone marks differentially regulates the activity and specificity of polycomb repressive complex 2 (PRC2).Proc. Natl. Acad. Sci. USA107, 19266-71 (2010).
49. Dhayalan, A., Kudithipudi, S., Rathert, P. & Jeltsch, A.Specificity analysis-based identification of new methylation targets of the SET7/9 protein lysine methyltransferase.Chem. Biol. 18, 111-20 (2011).
50. Takawa, M. et al.Histone lysine methyltransferase SETD8 promotes carcinogenesis by deregulating PCNA expression.Cancer Res. 72, 3217-27 (2012).
51. Kassner, I. et al.SET7/9-dependent methylation of ARTD1 at K508 stimulates poly-ADP-ribose formation after oxidative stress.Open Biol. 3, 120173 (2013).
52. Cloutier, P., Lavallée-Adam, M., Faubert, D., Blanchette, M. & Coulombe, B.A newly uncovered group of distantly related lysine methyltransferases preferentially interact with molecular chaperones to regulate their activity.PLoS Genet. 9, e1003210 (2013).
53. Estève, P.O. et al.Regulation of DNMT1 stability through SET7-mediated lysine methylation in mammalian cells.Proc. Natl. Acad. Sci. USA106, 5076-81 (2009).
54. Wang, J. et al.The lysine demethylase LSD1 (KDM1) is required for maintenance of global DNA methylation.Nat. Genet. 41, 125-9 (2009).
55. Chang, Y. et al.MPP8 mediates the interactions between DNA methyltransferase Dnmt3a and H3K9 methyltransferase GLP/G9a.Nat. Commun. 2, 533 (2011).
56. Wang, D. et al.Methylation of SUV39H1 by SET7/9 results in heterochromatin relaxation and genome instability.Proc. Natl. Acad. Sci. USA110, 5516-21 (2013).
57. Sampath, S.C. et al.Methylation of a histone mimic within the histone methyltransferase G9a regulates protein complex assembly. Mol. Cell27, 596-608 (2007).
58. Chin, H.G. et al.Automethylation of G9a and its implication in wider substrate specificity and HP1 binding.Nucleic Acids Res. 35, 7313-23 (2007).
59.Kernstock, S. et al.Lysine methylation of VCP by a member of a novel human protein methyltransferase family.Nat. Commun. 3, 1038 (2012).
60. Magen, S. et al.Human calmodulin methyltransferase, expression, activity on calmodulin, and Hsp90 dependence.PLoS One7, e52425 (2012).
61. Masatsugu, T. & Yamamoto, K.Multiple lysine methylation of PCAF by Set9 methyltransferase.Biochem. Biophys. Res. Commun. 381, 22-6 (2009).
62. Rathert, P. et al.Protein lysine methyltransferase G9a acts on non-histone targets.Nat. Chem. Biol. 4(6), 344-6 (2008).
63. Liu, L. et al.Probing the invasiveness of prostate cancer cells in a 3D microfabricated landscape.Proc. Natl. Acad. Sci. USA. 108, 6853-6 (2011).
64. Levy, D. et al.A proteomic approach for the identification of novel lysine methyltransferase substrates.Epigenetics Chromatin. 4, 19 (2011).
65. Abu-Farha, M. et al.Proteomic analyses of the SMYD family interactomes identify HSP90 as a novel target for SMYD2.J. Mol. Cell. Biol. 3, 301-8 (2011).
66. Cho, H.S. et al.Enhanced HSP70 lysine methylation promotes proliferation of cancer cells through activation of Aurora kinase B.Nat. Commun. 3, 1072 (2012).
67. Sitaramayya, A., Wright, L.S. &Siegel, F.L.Enzymatic methylationof calmodulin in rat brain cytosol.J. Biol. Chem.255, 8894–8900 (1980).
68. Van Duyne, R. et al.Lysine methylation of HIV-1 Tat regulates transcriptional activity of the viral LTR.Retrovirology5, 40 (2008).
69. Pagans, S. et al.The Cellular lysine methyltransferase Set7/9-KMT7 binds HIV-1 TAR RNA, monomethylates the viral transactivator Tat, and enhances HIV transcription.Cell Host Microbe. 7, 234-44 (2010).
70. Dhami, G.K. et al.Dynamic methylation of Numb by Set8 regulates its binding to p53 and apoptosis.Mol. Cell50, 565-76 (2013).
71. Mazur, P.K. et al. SMYD3 links lysine methylation of MAP3K2 to Ras-driven cancer. Nature 510, 283-287 (2014).
72. Kunizaki, M. et al.The lysine 831 of vascular endothelial growth factor receptor 1 is a novel target of methylation by SMYD3.Cancer Res. 67, 10759-65 (2007).
73. Lu, P. et al. PRMT4 blocks myeloid differentiation by assembling a methyl-RUNX1-dependent repressor complex. Cell Reports5, 1625-1638 (2013).
74. Zhao, X. et al. Methylation of RUNX1 by PRMT1 abrogates SIN3A binding and potentiates its transcriptional activity. Genes Dev. 22, 640-653 (2008).
75. Cho, E. et al. Arginine methylation controls growth regulation by E2F-1. EMBO J. 31, 1785-1797 (2012).
76. Zheng, S. et al. Arginine methylation-dependent reader-writer interplay governs growth control by E2F-1. Mol. Cell52, 37-51 (2013).
77. Taylor, R.H. et al. Arginine methylation regulates telomere length and stability. Mol. Cell. Biol. 29, 4918-4934 (2009).
78. Lin, W.J. et al. The mammalian immediate-early TIS2 protein and the leukemia-associated BTG1 protein interact with a protein-arginine N-methyltransferase. J. Biol. Chem. 271, 15034-15044 (1996).
79.Tang, J., Kao, P.N. & Herschman, H.R. Protein-arginine methyltransferase I, the predominant protein-arginine methyltransferase in cells, interacts with and is regulated by interleukin enhancer-binding factor 3. J. Biol. Chem. 275, 19866-19876 (2000).
80. Le Romancer, M. et al. Regulation of estrogen signaling through arginine methylation by PRMT1. Mol. Cell31, 212-221 (2008).
81. Qi, C. et al. Identification of PRMT2 as a coactivator for estrogen receptor alpha. J. Biol. Chem. 277, 28624-28630 (2002).
82. Jobert, L., Argentini, M. & Tora, L. PRMT1 mediated methylation of TAF15 is required for its positive gene regulatory function. Exp. Cell Res. 315, 1273-1286 (2009).
83. Teyssier, C. et al. Protein arginine methylation in estrogen signaling and estrogen-related cancers. Trends Endocrinol. Metab. 21, 181-189 (2010).
84. Ito, T. et al. Arginine methyltransferase CARM1/PRMT4 regulates endochondral ossification. BMC Dev. Biol.9, 47 (2009).
85. Cheng, D., Cote, J., Shaaban, S. & Bedford, M.T. The arginine methyltransferase CARM1 regulates the coupling of transcription and mRNA processing.Mol. Cell25, 71–83 (2007).
86.Karhanis, V. et al. Versatility of PRMT5-induced methylation in growth control and development. Trends Biochem. Sci. 36, 633-541 (2011).
87.Bandyopadhyay, S. et al. HOXA9 methylation by PRMT5 is essential for endothelial cell expression of leukocyte adhesion molecules.Mol. Cell. Biol.32, 1202–13 (2012).
88. Wei, H. et al. PRMT5 dimethylates R30 of the p65 subunit to activate NFκB.Proc. Natl. Acad. Sci. USA.110, 13516–21 (2013).
89. Wang, L. et al. CARM1 methylates chromatin remodeling factor BAF155 to enhance tumor progression and metastasis. Cancer Cell25, 21-36 (2014).
90. Sgarra, R.et al. The AT-hook of the chromatin architectural transcription factor high mobility group A1a is arginine-methylated by protein arginine methyltransferase 6.J. Biol. Chem.281, 3764–72 (2006).
91. Boisvert, F.M., Rhie, A., Richard, S. & Doherty, A.J. The GAR motif of 53BP1 is arginine methylated by PRMT1 and is necessary for 53BP1 DNA binding activity.Cell Cycle4, 1834–41 (2005).
92. Boisvert, F.M., Déry, U., Masson, J.Y. & Richard, S. Arginine methylation of MRE11 by PRMT1 is required for DNA damage checkpoint control.Genes Dev.19, 671–6 (2005).
93. El-Andaloussi, N. et al. Arginine methylation regulates DNA polymerase beta.Mol. Cell22, 51–62 (2006).
94. Lee, J. & Bedford, M.T. PABP1 identified as an arginine methyltransferase substrate using high-density protein arrays.EMBO Rep.3, 268–73 (2002).
95. Butler, J.S., Zurita-Lopez, C.I., Clarke, S.G., Bedford, M.T. & Dent, S.Y. Protein-arginine methyltransferase 1 (PRMT1) methylates Ash2L, a shared component of mammalian histone H3K4 methyltransferase complexes.J. Biol. Chem.286, 12234–44 (2011).
96. Yang, M. et al. Caenorhabditis elegans protein arginine methyltransferase PRMT-5 negatively regulates DNA damage-induced apoptosis.PLoS Genet.5, e1000514 (2009).
97. Yamamoto, T. et al. Reduced methylation of PFKFB3 in cancer cells shunts glucose toward the pentose phosphate pathway. Nat. Commun.5, 3480 (2014).
98. Buss, H. et al. Phosphorylation of serine 468 by GSK-3beta negatively regulates basal p65 NFkappaB activity.J. Biol. Chem.279, 49571–4 (2004).
99. Boulanger, M.C. et al. Methylation of Tat by PRMT6 regulates human immunodeficiency virus type 1 gene expression.J. Virol.79, 124–31 (2005).
100. Lin, W.J., Gary, J.D., Yang, M.C., Clarke, S. & Herschman, H.R. The mammalian immediate-early TIS21 protein and the leukemia-associated BTG1 protein interact with a protein-arginine N-methyltransferase.J. Biol. Chem.271, 15034–44 (1996).
101. Abramovich, C., Yakobson, B., Chebath, J. & Revel, M. A protein-arginine methyltransferase binds to the intracytoplasmic domain of the IFNAR1 chain in the type I interferon receptor.EMBO J.16, 260–6 (1997).
102. Infantino, S. et al. Arginine methylation of the B cell antigen receptor promotes differentiation.J. Exp. Med.207, 711–9 (2010).
103. Martin, G. et al. Arginine methylation in subunits of mammalian pre-mRNA cleavage factor I.RNA.16, 1646–59 (2010).
104. Baldwin, G.S. & Carnegie, P.R. Specific enzymic methylation of an arginine in the experimental allergic encephalomyelitis protein from human myelin.Science171, 579–81 (1971).
105. Sayegh, J., Webb, K., Cheng, D., Bedford, M.T. & Clarke, S.G. Regulation of protein arginine methyltransferase 8 (PRMT8) activity by its N-terminal domain.J. Biol. Chem.282, 36444–53 (2007).
106. Powers, M.A., Fay, M.M., Factor, R.E., Welm, A.L. & Ullman, K.S. Protein arginine methyltransferase 5 accelerates tumor growth by arginine methylation of the tumor suppressor programmed cell death 4.Cancer Res.71, 5579–87 (2011).
107. Rajpurohit, R., Lee, S.O., Park, J.O., Paik, W.K. & Kim, S. Enzymatic methylation of recombinant heterogeneous nuclear RNP protein A1. Dual substrate specificity for S-adenosylmethionine, histone-arginine N-methyltransferase. J. Biol. Chem.269, 1075–82 (1994).
108. Kwak, Y.T. et al. Methylation of SPT5 regulates its interaction with RNA polymerase II and transcriptional elongation properties.Mol. Cell11, 1055–66 (2003).
109. Herrmann, F., Bossert, M., Schwander, A., Akgün, E. & Fackelmayer, F.O. Arginine methylation of scaffold attachment factor A by heterogeneous nuclear ribonucleoprotein particle-associated PRMT1.J. Biol. Chem. 279, 48774–9 (2004).
110. Dolzhanskaya, N., Merz, G. & Denman, R.B. Alternative splicing modulates protein arginine methyltransferase-dependent methylation of fragile X syndrome mental retardation protein.Biochemistry45, 10385–93 (2006).
111. Rho, J., Choi, S., Jung, C.R. & Im, D.S. Arginine methylation of Sam68 and SLM proteins negatively regulates their poly(U) RNA binding activity.Arch. Biochem. Biophys.466, 49–57 (2007).
112. Swiercz, R., Cheng, D., Kim, D. & Bedford, M.T. Ribosomal protein rpS2 is hypomethylated in PRMT3-deficient mice.J. Biol. Chem.282, 16917–23 (2007).
113.Brahms, H. et al. The C-terminal RG dipeptide repeats of the spliceosomal Sm proteins D1 and D3 contain symmetrical dimethylarginines, which form a major B-cell epitope for anti-Sm autoantibodies.J. Biol. Chem.275, 17122–9 (2000).
114. Shire, K. et al. Regulation of the EBNA1 Epstein-Barr virus protein by serine phosphorylation and arginine methylation.J. Virol.80, 5261–72 (2006).
115. Barth, S. et al. Epstein-Barr virus nuclear antigen 2 binds via its methylated arginine-glycine repeat to the survival motor neuron protein.J. Virol.77, 5008–13 (2003).
116. Kwak, Y.T. et al. Methylation of SPT5 regulates its interaction with RNA polymerase II and transcriptional elongation properties.Mol. Cell 11, 1055–66 (2003).
117. Kim, J.D., Kako, K., Kakiuchi, M., Park, G.G. & Fukamizu, A. EWS is a substrate of type I protein arginine methyltransferase, PRMT8.Int. J. Mol. Med.22, 309–15 (2008).
NATURE REVIEWS |MOLECULAR CELL BIOLOGY