S-adenosyl methionine is necessary for inhibition of the methyltransferase G9a by the lysine 9 to methionine mutation on histone H3

Proceedings of the National Academy of Sciences of the United States of America

Volumn 113, Issue 22, 2016, Pages 6282-6287

  Jayaram, Hariharan ^a   Hoelper, Dominik ^b,c   Jain, Siddhant U ^b,c   Cantone, Nico ^a   Lundgren, Stefan M ^b,c   Poy, Florence ^a   Allis, C David ^d   Cummings, Richard ^a   Bellon, Steven ^a   Lewis, Peter W ^b,c  

^a Department of Structural Biology   (United States)

^b UNIVERSITY OF WISCONSIN MADISON   (United States)

^c UNIVERSITY OF WISCONSIN SCHOOL OF MEDICINE AND PUBLIC HEALTH   (United States)

^d ROCKEFELLER UNIVERSITY   (United States)

Author keywords

EHMT2; G9a; H3K9me3; K to M; Oncohistone

Indexed keywords

HISTONE H3; LYSINE; METHIONINE; METHYLTRANSFERASE; METHYLTRANSFERASE G9A; ONCOPROTEIN; POLYCOMB REPRESSIVE COMPLEX 2; S ADENOSYLMETHIONINE; TRITHORAX DOMAIN METHYLTRANSFERASE; UNCLASSIFIED DRUG; HISTONE; HISTONE LYSINE METHYLTRANSFERASE; PEPTIDE FRAGMENT;

AMINO ACID SUBSTITUTION; ARTICLE; BINDING SITE; CARCINOGENESIS; CHROMATIN STRUCTURE; COMPETITIVE INHIBITION; ENZYME ACTIVITY; ENZYME INHIBITION; HISTONE METHYLATION; HUMAN; IC50; IN VITRO STUDY; IN VIVO STUDY; ISOTHERMAL TITRATION CALORIMETRY; MUTATION; PRIORITY JOURNAL; PROTEIN CONFORMATION; RELATIVE BINDING AFFINITY; TRANSGENE; ANTAGONISTS AND INHIBITORS; CHEMISTRY; ENZYME SPECIFICITY; GENETICS; X RAY CRYSTALLOGRAPHY;

CRYSTALLOGRAPHY, X-RAY; HISTONE-LYSINE N-METHYLTRANSFERASE; HISTONES; HUMANS; LYSINE; METHIONINE; MUTATION; PEPTIDE FRAGMENTS; S-ADENOSYLMETHIONINE; SUBSTRATE SPECIFICITY;

EID: 84973171115     PISSN: 00278424     EISSN: 10916490     Source Type: Journal    
DOI: 10.1073/pnas.1605523113     Document Type: Article

References (26)

1. Schwartzentruber J, et al. (2012) Driver mutations in histone H3.3 and chromatin remodelling genes in paediatric glioblastoma. Nature 482(7384):226-231.
2. Wu G, et al.; St. Jude Children's Research Hospital-Washington University Pediatric Cancer Genome Project (2014) The genomic landscape of diffuse intrinsic pontine glioma and pediatric non-brainstem high-grade glioma. Nat Genet 46(5):444-450.
3. Behjati S, et al. (2013) Distinct H3F3A and H3F3B driver mutations define chondroblastoma and giant cell tumor of bone. Nat Genet 45(12):1479-1482.
4. Bender S, et al. (2013) Reduced H3K27me3 and DNA hypomethylation are major drivers of gene expression in K27M mutant pediatric high-grade gliomas. Cancer Cell 24(5):660-672.
5. Brown ZZ, et al. (2014) Strategy for "detoxification" of a cancer-derived histone mutant based on mapping its interaction with the methyltransferase PRC2. J Am Chem Soc 136(39):13498-13501.
6. Brown ZZ, Müller MM, Kong HE, Lewis PW, Muir TW (2015) Targeted histone peptides: Insights into the spatial regulation of the methyltransferase PRC2 by using a surrogate of heterotypic chromatin. Angew Chem Int Ed Engl 54(22):6457-6461.
7. Lewis PW, et al. (2013) Inhibition of PRC2 activity by a gain-of-function H3 mutation found in pediatric glioblastoma. Science 340(6134):857-861.
8. Bechet D, et al. (2014) Specific detection of methionine 27 mutation in histone 3 variants (H3K27M) in fixed tissue from high-grade astrocytomas. Acta Neuropathol 128(5):733-741.
9. Venneti S, et al. (2014) A sensitive and specific histopathologic prognostic marker for H3F3A K27M mutant pediatric glioblastomas. Acta Neuropathol 128(5):743-753.
10. Castel D, et al. (2015) Histone H3F3A and HIST1H3B K27M mutations define two subgroups of diffuse intrinsic pontine gliomas with different prognosis and phenotypes. Acta Neuropathol 130(6):815-827.
11. Tachibana M, Sugimoto K, Fukushima T, Shinkai Y (2001) Set domain-containing protein, G9a, is a novel lysine-preferring mammalian histone methyltransferase with hyperactivity and specific selectivity to lysines 9 and 27 of histone H3. J Biol Chem 276(27):25309-25317.
12. Di Giacomo M, Comazzetto S, Sampath SC, Sampath SC, O'Carroll D (2014) G9a cosuppresses LINE1 elements in spermatogonia. Epigenetics Chromatin 7:24.
13. Leung DC, et al. (2011) Lysine methyltransferase G9a is required for de novo DNA methylation and the establishment, but not the maintenance, of proviral silencing. Proc Natl Acad Sci USA 108(14):5718-5723.
14. Maksakova IA, et al. (2013) Distinct roles of KAP1, HP1 and G9a/GLP in silencing of the two-cell-specific retrotransposon MERVL in mouse ES cells. Epigenetics Chromatin 6(1):15.
15. Chen MW, et al. (2010) H3K9 histone methyltransferase G9a promotes lung cancer invasion and metastasis by silencing the cell adhesion molecule Ep-CAM. Cancer Res 70(20):7830-7840.
16. Huang J, et al. (2010) G9a and Glp methylate lysine 373 in the tumor suppressor p53. J Biol Chem 285(13):9636-9641.
17. Lehnertz B, et al. (2014) The methyltransferase G9a regulates HoxA9-dependent transcription in AML. Genes Dev 28(4):317-327.
18. Wu H, et al. (2010) Structural biology of human H3K9 methyltransferases. PLoS One 5(1):e8570.
19. Kubicek S, et al. (2007) Reversal of H3K9me2 by a small-molecule inhibitor for the G9a histone methyltransferase. Mol Cell 25(3):473-481.
20. Lin Y, et al. (2012) Detecting S-adenosyl-L-methionine-induced conformational change of a histone methyltransferase using a homogeneous time-resolved fluorescence-based binding assay. Anal Biochem 423(1):171-177.
21. Sweis RF, et al. (2014) Discovery and development of potent and selective inhibitors of histone methyltransferase g9a. ACS Med Chem Lett 5(2):205-209.
22. Barsyte-Lovejoy D, et al. (2014) (R)-PFI-2 is a potent and selective inhibitor of SETD7 methyltransferase activity in cells. Proc Natl Acad Sci USA 111(35):12853-12858.
23. Rathert P, et al. (2008) Protein lysine methyltransferase G9a acts on non-histone targets. Nat Chem Biol 4(6):344-346.
24. Wu G, et al.; St. Jude Children's Research Hospital-Washington University Pediatric Cancer Genome Project (2012) Somatic histone H3 alterations in pediatric diffuse intrinsic pontine gliomas and non-brainstem glioblastomas. Nat Genet 44(3):251-253.
25. Jiao L, Liu X (2015) Structural basis of histone H3K27 trimethylation by an active polycomb repressive complex 2. Science 350(6258):aac4383.
26. Lewis PW, Allis CD (2013) Poisoning the "histone code" in pediatric gliomagenesis. Cell Cycle 12(20):3241-3242.