DNMT3A R882 mutants interact with polycomb proteins to block haematopoietic stem and leukaemic cell differentiation

Nature Communications

Volumn 7, Issue , 2016, Pages

  Koya, Junji ^a   Kataoka, Keisuke ^a   Sato, Tomohiko ^a,b   Bando, Masashige ^c   Kato, Yuki ^c   Tsuruta Kishino, Takako ^a   Kobayashi, Hiroshi ^a   Narukawa, Kensuke ^a   Miyoshi, Hiroyuki ^d   Shirahige, Katsuhiko ^c   Kurokawa, Mineo ^a,b  

^a UNIVERSITY OF TOKYO   (Japan)

^b UNIVERSITY OF TOKYO HOSPITAL   (Japan)

^c UNIVERSITY OF TOKYO   (Japan)

^d RIKEN BIORESOURCE CENTER   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

BMI1 PROTEIN; DNA METHYLTRANSFERASE 3A; MUTANT PROTEIN; TRANSCRIPTION FACTOR FKHR; TRANSCRIPTION FACTOR HOXA9; TRANSCRIPTION FACTOR PU 1; TRANSCRIPTION FACTOR RUNX1; DNA (CYTOSINE 5) METHYLTRANSFERASE; POLYCOMB GROUP PROTEIN; PROTEIN BINDING; RETINOIC ACID; RNF2 PROTEIN, HUMAN;

BIOTRANSFORMATION; CANCER; EXPERIMENTAL STUDY; GENE EXPRESSION; GENETIC ANALYSIS; METHYLATION; MOLECULAR ANALYSIS; MUTATION; PROTEIN; RODENT;

ANIMAL CELL; ANIMAL EXPERIMENT; ARTICLE; CEBPA GENE; CEBPE GENE; CELL DIFFERENTIATION; CONTROLLED STUDY; CPG ISLAND; DNA METHYLATION; DOWN REGULATION; ENZYME BINDING; FEMALE; GENE; GENE EXPRESSION; GENE MUTATION; HEMATOPOIETIC STEM CELL; IN VITRO STUDY; LEUKEMIA CELL; MALIGNANT TRANSFORMATION; MOUSE; NONHUMAN; PROMOTER REGION; ACUTE MYELOID LEUKEMIA; ANIMAL; BONE MARROW CELL; C57BL MOUSE; CELL CULTURE; CELL TRANSFORMATION; DRUG EFFECTS; ENZYMOLOGY; GENE SILENCING; GENETICS; METABOLISM; MUTATION; PATHOLOGY;

MURINAE;

ANIMALS; BONE MARROW CELLS; CELL DIFFERENTIATION; CELL TRANSFORMATION, NEOPLASTIC; CELLS, CULTURED; DNA (CYTOSINE-5-)-METHYLTRANSFERASE; DNA METHYLATION; DOWN-REGULATION; GENE SILENCING; HEMATOPOIETIC STEM CELLS; LEUKEMIA, MYELOID, ACUTE; MICE, INBRED C57BL; MUTANT PROTEINS; MUTATION; POLYCOMB REPRESSIVE COMPLEX 1; POLYCOMB-GROUP PROTEINS; PROTEIN BINDING; TRETINOIN;

EID: 84961665597     PISSN: None     EISSN: 20411723     Source Type: Journal    
DOI: 10.1038/ncomms10924     Document Type: Article

References (64)

1. Ley, T. J. et al. DNMT3A mutations in acute myeloid leukaemia. N. Engl. J. Med. 363, 2424-2433 (2010).
2. Yan, X. J. et al. Exome sequencing identifies somatic mutations of DNA methyltransferase gene DNMT3A in acute monocytic leukemia. Nat. Genet. 43, 309-315 (2011).
3. Thol, F. et al. Incidence and prognostic influence of DNMT3A mutations in acute myeloid leukemia. J. Clin. Oncol. 29, 2889-2896 (2011).
4. Marcucci, G. et al. Age-related prognostic impact of different types of DNMT3A mutations in adults with primary cytogenetically normal acute myeloid leukemia. J. Clin. Oncol. 30, 742-750 (2012).
5. Chen, T., Ueda, Y., Dodge, J. E., Wang, Z., Li, E. Establishment and maintenance of genomic methylation patterns in mouse embryonic stem cells by Dnmt3a and Dnmt3b. Mol. Cell. Biol. 23, 5594-5605 (2003).
6. Holz-Schietinger, C., Matje, D. M., Reich, N. O. Mutations in DNA methyltransferase (DNMT3A) observed in acute myeloid leukemia patients disrupt processive methylation. J. Biol. Chem. 287, 30941-30951 (2012).
7. Russler-Germain, D. A. et al. The R882H DNMT3A mutation associated with AML dominantly inhibits wild-type DNMT3A by blocking its ability to form active tetramers. Cancer Cell 25, 442-454 (2014).
8. Cancer Genome Atlas Research N. Genomic and epigenomic landscapes of adult de novo acute myeloid leukemia. N. Engl. J. Med. 368, 2059-2074 (2013).
9. Challen, G. A. et al. Dnmt3a is essential for hematopoietic stem cell differentiation. Nat. Genet. 44, 23-31 (2012).
10. Shlush, L. I. et al. Identification of pre-leukaemic haematopoietic stem cells in acute leukaemia. Nature 506, 328-333 (2014).
11. Xie, M. et al. Age-related mutations associated with clonal hematopoietic expansion and malignancies. Nat. Med. 20, 1472-1478 (2014).
12. Vire, E. et al. The Polycomb group protein EZH2 directly controls DNA methylation. Nature 439, 871-874 (2006).
13. Mohammad, H. P. et al. Polycomb CBX7 promotes initiation of heritable repression of genes frequently silenced with cancer-specific DNA hypermethylation. Cancer Res. 69, 6322-6330 (2009).
14. Zhao, Q. et al. PRMT5-mediated methylation of histone H4R3 recruits DNMT3A, coupling histone and DNA methylation in gene silencing. Nat. Struct. Mol. Biol. 16, 304-311 (2009).
15. Widschwendter, M. et al. Epigenetic stem cell signature in cancer. Nat. Genet. 39, 157-158 (2007).
16. Ohm, J. E. et al. A stem cell-like chromatin pattern may predispose tumor suppressor genes to DNA hypermethylation and heritable silencing. Nat. Genet. 39, 237-242 (2007).
17. Schlesinger, Y. et al. Polycomb-mediated methylation on Lys27 of histone H3 pre-marks genes for de novo methylation in cancer. Nat. Genet. 39, 232-236 (2007).
18. Villa, R. et al. Role of the polycomb repressive complex 2 in acute promyelocytic leukemia. Cancer Cell 11, 513-525 (2007).
19. Boukarabila, H. et al. The PRC1 Polycomb group complex interacts with PLZF/RARA to mediate leukemic transformation. Genes Dev. 23, 1195-1206 (2009).
20. Neff, T. et al. Polycomb repressive complex 2 is required for MLL-AF9 leukemia. Proc. Natl Acad. Sci USA 109, 5028-5033 (2012).
21. Chambers, S. M. et al. Hematopoietic fingerprints: an expression database of stem cells and their progeny. Cell Stem Cell 1, 578-591 (2007).
22. Xu, J. et al. DNMT3A Arg882 mutation drives chronic myelomonocytic leukemia through disturbing gene expression/DNA methylation in hematopoietic cells. Proc. Natl Acad. Sci USA 111, 2620-2625 (2014).
23. Rosenbauer, F., Tenen, D. G. Transcription factors in myeloid development: balancing differentiation with transformation. Nat. Rev. Immunol. 7, 105-117 (2007).
24. Shen, Y. et al. Gene mutation patterns and their prognostic impact in a cohort of 1185 patients with acute myeloid leukemia. Blood 118, 5593-5603 (2011).
25. Kallin, E. M. et al. Genome-wide uH2A localization analysis highlights Bmi1-dependent deposition of the mark at repressed genes. PLoS Genet. 5, e1000506 (2009).
26. Gao, Z. et al. PCGF homologs, CBX proteins, and RYBP define functionally distinct PRC1 family complexes. Mol. Cell 45, 344-356 (2012).
27. Tavares, L. et al. RYBP-PRC1 complexes mediate H2A ubiquitylation at polycomb target sites independently of PRC2 and H3K27me3. Cell 148, 664-678 (2012).
28. Hollink, I. H. et al. Low frequency of DNMT3A mutations in pediatric AML, and the identification of the OCI-AML3 cell line as an in vitro model. Leukemia 26, 371-373 (2012).
29. Park, I. K. et al. Bmi-1 is required for maintenance of adult self-renewing haematopoietic stem cells. Nature 423, 302-305 (2003).
30. Iwama, A. et al. Enhanced self-renewal of hematopoietic stem cells mediated by the polycomb gene product Bmi-1. Immunity 21, 843-851 (2004).
31. Tiacci, E. et al. The NPM1 wild-type OCI-AML2 and the NPM1-mutated OCIAML3 cell lines carry DNMT3A mutations. Leukemia 26, 554-557 (2012).
32. Matkovic, K., Brugnoli, F., Bertagnolo, V., Banfic, H., Visnjic, D. The role of the nuclear Akt activation and Akt inhibitors in all-trans-retinoic aciddifferentiated HL-60 cells. Leukemia 20, 941-951 (2006).
33. Lin, J. et al. Recurrent DNMT3A R882 mutations in Chinese patients with acute myeloid leukemia and myelodysplastic syndrome. PLoS ONE 6, e26906 (2011).
34. Kroon, E. et al. Hoxa9 transforms primary bone marrow cells through specific collaboration with Meis1a but not Pbx1b. EMBO J. 17, 3714-3725 (1998).
35. Okano, M., Bell, D. W., Haber, D. A., Li, E. DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development. Cell 99, 247-257 (1999).
36. Hou, H. A. et al. DNMT3A mutations in acute myeloid leukemia: stability during disease evolution and clinical implications. Blood 119, 559-568 (2012).
37. Wakita, S. et al. Mutations of the epigenetics-modifying gene (DNMT3a, TET2, IDH1/2) at diagnosis may induce FLT3-ITD at relapse in de novo acute myeloid leukemia. Leukemia 27, 1044-1052 (2013).
38. Busque, L. et al. Recurrent somatic TET2 mutations in normal elderly individuals with clonal hematopoiesis. Nat. Genet. 44, 1179-1181 (2012).
39. Sakata-Yanagimoto, M. et al. Somatic RHOA mutation in angioimmunoblastic T cell lymphoma. Nat. Genet. 46, 171-175 (2014).
40. Vassiliou, G. S. et al. Mutant nucleophosmin and cooperating pathways drive leukemia initiation and progression in mice. Nat. Genet. 43, 470-475 (2011).
41. Antonchuk, J., Sauvageau, G., Humphries, R. K. HOXB4-induced expansion of adult hematopoietic stem cells ex vivo. Cell 109, 39-45 (2002).
42. Radulovic, V., de Haan, G., Klauke, K. Polycomb-group proteins in hematopoietic stem cell regulation and hematopoietic neoplasms. Leukemia 27, 523-533 (2013).
43. Sashida, G., Iwama, A. Epigenetic regulation of hematopoiesis. Int. J. Hematol. 96, 405-412 (2012).
44. Smith, L. L. et al. Functional crosstalk between Bmi1 and MLL/Hoxa9 axis in establishment of normal hematopoietic and leukemic stem cells. Cell Stem Cell 8, 649-662 (2011).
45. Yuan, J. et al. Bmi1 is essential for leukemic reprogramming of myeloid progenitor cells. Leukemia 25, 1335-1343 (2011).
46. Jacobs, J. J. et al. Bmi-1 collaborates with c-Myc in tumorigenesis by inhibiting c-Myc-induced apoptosis via INK4a/ARF. Genes Dev. 13, 2678-2690 (1999).
47. Chowdhury, M. et al. Expression of Polycomb-group (PcG) protein BMI-1 predicts prognosis in patients with acute myeloid leukemia. Leukemia 21, 1116-1122 (2007).
48. Shih, A. H., Abdel-Wahab, O., Patel, J. P., Levine, R. L. The role of mutations in epigenetic regulators in myeloid malignancies. Nat. Rev. Cancer 12, 599-612 (2012).
49. Morey, L., Aloia, L., Cozzuto, L., Benitah, S. A., Di Croce, L. RYBP and Cbx7 define specific biological functions of polycomb complexes in mouse embryonic stem cells. Cell Rep. 3, 60-69 (2013).
50. Iwasaki, H. et al. Distinctive and indispensable roles of PU.1 in maintenance of hematopoietic stem cells and their differentiation. Blood 106, 1590-1600 (2005).
51. Mueller, B. U. et al. Heterozygous PU.1 mutations are associated with acute myeloid leukemia. Blood 100, 998-1007 (2002).
52. Vangala, R. K. et al. The myeloid master regulator transcription factor PU.1 is inactivated by AML1-ETO in t(8;21) myeloid leukemia. Blood 101, 270-277 (2003).
53. Heuser, M. et al. MN1 overexpression induces acute myeloid leukemia in mice and predicts ATRA resistance in patients with AML. Blood 110, 1639-1647 (2007).
54. Mueller, B. U. et al. ATRA resolves the differentiation block in t(15;17) acute myeloid leukemia by restoring PU.1 expression. Blood 107, 3330-3338 (2006).
55. van der Lugt, N. M. et al. Posterior transformation, neurological abnormalities, and severe hematopoietic defects in mice with a targeted deletion of the bmi-1 proto-oncogene. Genes Dev. 8, 757-769 (1994).
56. Kurita, R. et al. Establishment of immortalized human erythroid progenitor cell lines able to produce enucleated red blood cells. PLoS ONE 8, e59890 (2013).
57. Kumaki, Y., Oda, M., Okano, M. QUMA: quantification tool for methylation analysis. Nucleic Acids Res. 36, W170-W175 (2008).
58. Habib, M. et al. DNA global hypomethylation in EBV-transformed interphase nuclei. Exp. Cell. Res. 249, 46-53 (1999).
59. Yoshimi, A. et al. Evi1 represses PTEN expression and activates PI3K/AKT/mTOR via interactions with polycomb proteins. Blood 117, 3617-3628 (2011).
60. Muntean, A. G. et al. The PAF complex synergizes with MLL fusion proteins at HOX loci to promote leukemogenesis. Cancer Cell 17, 609-621 (2010).
61. Deardorff, M. A. et al. HDAC8 mutations in Cornelia de Lange syndrome affect the cohesin acetylation cycle. Nature 489, 313-317 (2012).
62. Langmead, B., Trapnell, C., Pop, M., Salzberg, S. L. Ultrafast and memory-efficient alignment of short DNA sequences to the human genome. Genome Biol. 10, R25 (2009).
63. Nakato, R., Itoh, T., Shirahige, K. DROMPA: easy-to-handle peak calling and visualization software for the computational analysis and validation of ChIP-seq data. Genes Cells 18, 589-601 (2013).
64. McLean, C. Y. et al. GREAT improves functional interpretation of cisregulatory regions. Nat. Biotechnol. 28, 495-501 (2010).