DNMT3a epigenetic program regulates the HIF-2α oxygen-sensing pathway and the cellular response to hypoxia

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

Volumn 111, Issue 21, 2014, Pages 7783-7788

  Lachance, Gabriel ^a   Uniacke, James ^a   Audas, Timothy E ^a   Holterman, Chet E ^a   Franovic, Aleksandra ^a   Payette, Josianne ^a   Lee, Stephen ^a  

^a UNIVERSITY OF OTTAWA   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

DNA METHYLTRANSFERASE 3A; HYPOXIA INDUCIBLE FACTOR 2ALPHA; MESSENGER RNA; OXYGEN;

ADULT; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; ASTROCYTE; CELL DIFFERENTIATION; CELL GROWTH; CELL PROLIFERATION; CELL VIABILITY; CONTROLLED STUDY; CPG ISLAND; DNA METHYLATION; EPAS1 GENE; EPIGENETICS; FEMALE; GENE; GENE ACTIVATION; GENE SILENCING; GENETIC REGULATION; GLIOBLASTOMA; HUMAN; HUMAN CELL; HUMAN TISSUE; HYPOXIC CELL; KIDNEY CARCINOMA; KIDNEY TUBULE CELL; KIDNEY TUBULE EPITHELIUM; METHYLATION; MOUSE; NONHUMAN; OXYGEN DIFFUSION; OXYGEN SENSING; OXYGEN TENSION; PHENOTYPE; PLURIPOTENT STEM CELL; PRIMARY TUMOR; PRIORITY JOURNAL; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; SIGNAL TRANSDUCTION; TRANSIENT EXPRESSION; TUMOR MICROENVIRONMENT; TUMOR XENOGRAFT; WESTERN BLOTTING;

ANIMALS; BASIC HELIX-LOOP-HELIX TRANSCRIPTION FACTORS; CARCINOGENESIS; CELL HYPOXIA; CELL LINE, TUMOR; DNA (CYTOSINE-5-)-METHYLTRANSFERASE; DNA METHYLATION; EPIGENESIS, GENETIC; FEMALE; HUMANS; MICE; MICE, NUDE;

EID: 84901659554     PISSN: 00278424     EISSN: 10916490     Source Type: Journal    
DOI: 10.1073/pnas.1322909111     Document Type: Article

References (43)

1. Semenza GL (2012) Hypoxia-inducible factors in physiology and medicine. Cell 148(3): 399-408.
2. Semenza GL (2011) Oxygen sensing, homeostasis, and disease. N Engl J Med 365(6): 537-547.
3. Semenza GL (2010) HIF-1: Upstream and downstream of cancer metabolism. Curr Opin Genet Dev 20(1):51-56.
4. Ratcliffe PJ (2013) Oxygen sensing and hypoxia signalling pathways in animals: The implications of physiology for cancer. J Physiol 591(Pt 8):2027-2042.
5. Epstein AC, et al. (2001) C. elegans EGL-9 and mammalian homologs define a family of dioxygenases that regulate HIF by prolyl hydroxylation. Cell 107(1):43-54. (Pubitemid 32972036)
6. Bruick RK, McKnight SL (2001) A conserved family of prolyl-4-hydroxylases that modify HIF. Science 294(5545):1337-1340. (Pubitemid 33063099)
7. Ivan M, et al. (2001) HIFalpha targeted for VHL-mediated destruction by proline hy-droxylation: Implications for O2 sensing. Science 292(5516):464-468. (Pubitemid 32335941)
8. Jaakkola P, et al. (2001) Targeting of HIF-alpha to the von Hippel-Lindau ubiq-uitylation complex by O2-regulated prolyl hydroxylation. Science 292(5516):468-472. (Pubitemid 32335942)
9. Maxwell PH, et al. (1999) The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis. Nature 399(6733):271-275. (Pubitemid 29246458)
10. Majmundar AJ, Wong WJ, Simon MC (2010) Hypoxia-inducible factors and the response to hypoxic stress. Mol Cell 40(2):294-309.
11. Wiesener MS, et al. (1998) Induction of endothelial PAS domain protein-1 by hypoxia: Characterization and comparison with hypoxia-inducible factor-1alpha. Blood 92(7): 2260-2268. (Pubitemid 28452966)
12. Talks KL, et al. (2000) The expression and distribution of the hypoxia-inducible factors HIF-1alpha and HIF-2alpha in normal human tissues, cancers, and tumor-associated macrophages. Am J Pathol 157(2):411-421. (Pubitemid 30626905)
13. Mandriota SJ, et al. (2002) HIF activation identifies early lesions in VHL kidneys: Evidence for site-specific tumor suppressor function in the nephron. Cancer Cell 1(5):459-468. (Pubitemid 41039126)
14. Kim CM, et al. (2006) Expression of hypoxia inducible factor-1alpha and 2alpha in genetically distinct early renal cortical tumors. J Urol 175(5):1908-1914.
15. Kondo K, Klco J, Nakamura E, Lechpammer M, Kaelin WG, Jr. (2002) Inhibition of HIF is necessary for tumor suppression by the von Hippel-Lindau protein. Cancer Cell 1(3): 237-246. (Pubitemid 41039148)
16. Gordan JD, Bertout JA, Hu CJ, Diehl JA, Simon MC (2007) HIF-2alpha promotes hyp-oxic cell proliferation by enhancing c-Myc transcriptional activity. Cancer Cell 11(4): 335-347. (Pubitemid 46518312)
17. Kim WY, et al. (2009) HIF2alpha cooperates with RAS to promote lung tumorigenesis in mice. J Clin Invest 119(8):2160-2170.
18. Uniacke J, et al. (2012) An oxygen-regulated switch in the protein synthesis machinery. Nature 486(7401):126-129.
19. Wang Y, et al. (2009) Regulation of endocytosis via the oxygen-sensing pathway. Nat Med 15(3):319-324.
20. Franovic A, Holterman CE, Payette J, Lee S (2009) Human cancers converge at the HIF-2alpha oncogenic axis. Proc Natl Acad Sci USA 106(50):21306-21311.
21. Li Z, et al. (2009) Hypoxia-inducible factors regulate tumorigenic capacity of glioma stem cells. Cancer Cell 15(6):501-513.
22. Mazumdar J, et al. (2010) HIF-2alpha deletion promotes Kras-driven lung tumor development. Proc Natl Acad Sci USA 107(32):14182-14187.
23. Qing G, Simon MC (2009) Hypoxia inducible factor-2alpha: A critical mediator of aggressive tumor phenotypes. Curr Opin Genet Dev 19(1):60-66.
24. Lu C, Thompson CB (2012) Metabolic regulation of epigenetics. Cell Metab 16(1):9-17.
25. Jones PA (2012) Functions of DNA methylation: Islands, start sites, gene bodies and beyond. Nat Rev Genet 13(7):484-492.
26. Easwaran H, Baylin SB (2013) Epigenetic abnormalities in cancer find a "home on the range." Cancer Cell 23(1):1-3.
27. Dawson MA, Kouzarides T (2012) Cancer epigenetics: From mechanism to therapy. Cell 150(1):12-27.
28. Li E, Bestor TH, Jaenisch R (1992) Targeted mutation of the DNA methyltransferase gene results in embryonic lethality. Cell 69(6):915-926.
29. Okano M, Bell DW, Haber DA, Li E (1999) DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development. Cell 99(3):247-257. (Pubitemid 29519904)
30. Kaelin WG, Jr., McKnight SL (2013) Influence of metabolism on epigenetics and disease. Cell 153(1):56-69.
31. Feinberg AP, Ohlsson R, Henikoff S (2006) The epigenetic progenitor origin of human cancer. Nat Rev Genet 7(1):21-33. (Pubitemid 41828945)
32. Ley TJ, et al. (2010) DNMT3A mutations in acute myeloid leukemia. N Engl J Med 363(25):2424-2433.
33. Yan XJ, et al. (2011) Exome sequencing identifies somatic mutations of DNA methyltransferase gene DNMT3A in acute monocytic leukemia. Nat Genet 43(4):309-315.
34. Kim MS, Kim YR, Yoo NJ, Lee SH (2013) Mutational analysis of DNMT3Agene in acute leukemias and common solid cancers. APMIS 121(2):85-94.
35. Gao Q, et al. (2011) Deletion of the de novo DNA methyltransferase Dnmt3a promotes lung tumor progression. Proc Natl Acad Sci USA 108(44):18061-18066.
36. Russler-Germain DA, et al. (2014) The R882H DNMT3A mutation associated with AML dominantly inhibits wild-type DNMT3A by blocking its ability to form active tet-ramers. Cancer Cell 25(4):442-454.
37. Li E, Beard C, Jaenisch R (1993) Role for DNA methylation in genomic imprinting. Nature 366(6453):362-365. (Pubitemid 23349366)
38. Linhart HG, et al. (2007) Dnmt3b promotes tumorigenesis in vivo by gene-specific de novo methylation and transcriptional silencing. Genes Dev21(23):3110-3122. (Pubitemid 350223528)
39. Choi SH, et al. (2011) Identification of preferential target sites for human DNA methyltransferases. Nucleic Acids Res 39(1): 104-118.
40. Acker H, Carlsson J, Mueller-Klieser W, Sutherland RM (1987) Comparative pO2 measurements in cell spheroids cultured with different techniques. Br J Cancer 56(3):325-327. (Pubitemid 17158823)
41. Shen C, et al. (2011) Genetic and functional studies implicate HIF1alpha as a 14q kidney cancer suppressor gene. Cancer Discov 1(3):222-235.
42. Montagner M, et al. (2012) SHARP1 suppresses breast cancer metastasis by promoting degradation of hypoxia-inducible factors. Nature 487(7407):380-384.
43. Vanharanta S, et al. (2013) Epigenetic expansion of VHL-HIF signal output drives multiorgan metastasis in renal cancer. Nat Med 19(1):50-56.