Retinol and ascorbate drive erasure of Epigenetic memory and enhance reprogramming to naïve pluripotency by complementary mechanisms

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

Volumn 113, Issue 43, 2016, Pages 12202-12207

  Hore, Timothy Alexander ^a,b   Von Meyenn, Ferdinand ^a   Ravichandran, Mirunalini ^c   Bachman, Martin ^d   Ficz, Gabriella ^e   Oxley, David ^a   Santos, Fátima ^a   Balasubramanian, Shankar ^d   Jurkowski, Tomasz P ^c   Reik, Wolf ^a,f  

^a BABRAHAM INSTITUTE   (United Kingdom)

^b UNIVERSITY OF OTAGO   (New Zealand)

^c UNIVERSITY OF STUTTGART   (Germany)

^d UNIVERSITY OF CAMBRIDGE   (United Kingdom)

^e QUEEN MARY UNIVERSITY OF LONDON   (United Kingdom)

^f WELLCOME TRUST SANGER INSTITUTE   (United Kingdom)

Author keywords

DNA methylation; Epigenetic memory; Naive pluripotency; TET; Vitamin A C

Indexed keywords

5 HYDROXYMETHYLCYTOSINE; ASCORBIC ACID; GREEN FLUORESCENT PROTEIN; OCTAMER TRANSCRIPTION FACTOR 4; PROTEIN; RETINOL ACETATE; TEN ELEVEN TRANSLOCATION 2 PROTEIN; TEN ELEVEN TRANSLOCATION 3 PROTEIN; UNCLASSIFIED DRUG; 5 METHYLCYTOSINE; DIOXYGENASE; DNA BINDING PROTEIN; ONCOPROTEIN; RETINOIC ACID; RETINOL; TET2 PROTEIN, HUMAN; TET3 PROTEIN, HUMAN;

ANIMAL CELL; APPARENT DISSOCIATION CONSTANT; CATALYSIS; CHROMATIN IMMUNOPRECIPITATION; CLUSTERED REGULARLY INTERSPACED SHORT PALINDROMIC REPEAT; CONFERENCE PAPER; CONTROLLED STUDY; DECARBOXYLATION; DEMETHYLATION; DNA METHYLATION; DRUG POTENTIATION; ECTODERM; EMBRYO; ENZYME ACTIVITY; ENZYME LINKED IMMUNOSORBENT ASSAY; EPIGENETIC MEMORY; EPIGENETICS; HUMAN; HUMAN CELL; INDUCED PLURIPOTENT STEM CELL; MASS SPECTROMETRY; MEMORY; MOUSE; NONHUMAN; NUCLEAR REPROGRAMMING; OXIDATION; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN STABILITY; REPORTER GENE; STEM CELL CULTURE; ANIMAL; CELL DIFFERENTIATION; CYTOLOGY; DRUG EFFECTS; GENETIC EPIGENESIS; GENETICS; METABOLISM; REGENERATIVE MEDICINE;

5-METHYLCYTOSINE; ANIMALS; ASCORBIC ACID; CELL DIFFERENTIATION; DIOXYGENASES; DNA METHYLATION; DNA-BINDING PROTEINS; EPIGENESIS, GENETIC; HUMANS; INDUCED PLURIPOTENT STEM CELLS; MICE; PROTO-ONCOGENE PROTEINS; REGENERATIVE MEDICINE; TRETINOIN; VITAMIN A;

EID: 84992391011     PISSN: 00278424     EISSN: 10916490     Source Type: Journal    
DOI: 10.1073/pnas.1608679113     Document Type: Article

References (55)

1. Ficz G, et al. (2013) FGF signaling inhibition in ESCs drives rapid genome-wide demethylation to the epigenetic ground state of pluripotency. Cell Stem Cell 13(3):351-359.
2. Habibi E, et al. (2013) Whole-genome bisulfite sequencing of two distinct interconvertible DNA methylomes of mouse embryonic stem cells. Cell Stem Cell 13(3):360-369.
3. Leitch HG, et al. (2013) Naive pluripotency is associated with global DNA hypomethylation. Nat Struct Mol Biol 20(3):311-316.
4. Yamaji M, et al. (2013) PRDM14 ensures naive pluripotency through dual regulation of signaling and epigenetic pathways in mouse embryonic stem cells. Cell Stem Cell 12(3):368-382.
5. Theunissen TW, et al. (2014) Systematic identification of culture conditions for induction and maintenance of naive human pluripotency. Cell Stem Cell 15(4):471-487.
6. Lee HJ, Hore TA, Reik W (2014) Reprogramming the methylome: Erasing memory and creating diversity. Cell Stem Cell 14(6):710-719.
7. Hon GC, et al. (2013) Epigenetic memory at embryonic enhancers identified in DNA methylation maps from adult mouse tissues. Nat Genet 45(10):1198-1206.
8. Mikkelsen TS, et al. (2008) Dissecting direct reprogramming through integrative genomic analysis. Nature 454(7200):49-55.
9. Theunissen TW, et al. (2011) Nanog overcomes reprogramming barriers and induces pluripotency in minimal conditions. Curr Biol 21(1):65-71.
10. Jurkowski TP, Jeltsch A (2011) Burning off DNA methylation: New evidence for oxygendependent DNA demethylation. ChemBioChem 12(17):2543-2545.
11. Tahiliani M, et al. (2009) Conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA by MLL partner TET1. Science 324(5929):930-935.
12. Ficz G, et al. (2011) Dynamic regulation of 5-hydroxymethylcytosine in mouse ES cells and during differentiation. Nature 473(7347):398-402.
13. Ito S, et al. (2011) Tet proteins can convert 5-methylcytosine to 5-formylcytosine and 5-carboxylcytosine. Science 333(6047):1300-1303.
14. von Meyenn F, et al. (2016) Impairment of DNA methylation maintenance is the main cause of global demethylation in naive embryonic stem cells. Mol Cell 62(6):848-861.
15. Williams K, et al. (2011) TET1 and hydroxymethylcytosine in transcription and DNA methylation fidelity. Nature 473(7347):343-348.
16. Costa Y, et al. (2013) NANOG-dependent function of TET1 and TET2 in establishment of pluripotency. Nature 495(7441):370-374.
17. Gao Y, et al. (2013) Replacement of Oct4 by Tet1 during iPSC induction reveals an important role of DNA methylation and hydroxymethylation in reprogramming. Cell Stem Cell 12(4):453-469.
18. Doege CA, et al. (2012) Early-stage epigenetic modification during somatic cell reprogramming by Parp1 and Tet2. Nature 488(7413):652-655.
19. Blaschke K, et al. (2013) Vitamin C induces Tet-dependent DNA demethylation and a blastocyst-like state in ES cells. Nature 500(7461):222-226.
20. Chen J, et al. (2013) Vitamin C modulates TET1 function during somatic cell reprogramming. Nat Genet 45(12):1504-1509.
21. Minor EA, Court BL, Young JI, Wang G (2013) Ascorbate induces ten-eleven translocation (Tet) methylcytosine dioxygenase-mediated generation of 5-hydroxymethylcytosine. J Biol Chem 288(19):13669-13674.
22. Dickson KM, Gustafson CB, Young JI, Züchner S, Wang G (2013) Ascorbate-induced generation of 5-hydroxymethylcytosine is unaffected by varying levels of iron and 2-oxoglutarate. Biochem Biophys Res Commun 439(4):522-527.
23. Yin R, et al. (2013) Ascorbic acid enhances Tet-mediated 5-methylcytosine oxidation and promotes DNA demethylation in mammals. J Am Chem Soc 135(28):10396-10403.
24. Yang J, et al. (2014) Signalling through retinoic acid receptors is required for reprogramming of both MEFs and EpiSCs to iPSCs. Stem Cells 33(5):1390-1404.
25. Chung T-L, et al. (2010) Vitamin C promotes widespread yet specific DNA demethylation of the epigenome in human embryonic stem cells. Stem Cells 28(10):1848-1855.
26. Kuiper C, Vissers M C M (2014) Ascorbate as a co-factor for Fe- and 2-oxoglutarate dependent dioxygenases: Physiological activity in tumor growth and progression. Front Oncol 4:359.
27. Myllylä R, Majamaa K, Günzler V, Hanauske-Abel HM, Kivirikko KI (1984) Ascorbate is consumed stoichiometrically in the uncoupled reactions catalyzed by prolyl 4-hydroxylase and lysyl hydroxylase. J Biol Chem 259(9):5403-5405.
28. De Jong L, Albracht SPJ, Kemp A (1982) Prolyl 4-hydroxylase activity in relation to the oxidation state of enzyme-bound iron: The role of ascorbate in peptidyl proline hydroxylation. Biochim Biophys Acta 704(2):326-332.
29. 2 in aqueous solution: Basic principles and a simple heuristic description. Chemosphere 68(11):2080-2084.
30. Petrat F, et al. (2003) Reduction of Fe (III) ions complexed to physiological ligands by lipoyl dehydrogenase and other flavoenzymes in vitro: Implications for an enzymatic reduction of Fe (III) ions of the labile iron pool. J Biol Chem 278(47):46403-46413.
31. Epsztejn S, Kakhlon O, Glickstein H, Breuer W, Cabantchik I (1997) Fluorescence analysis of the labile iron pool of mammalian cells. Anal Biochem 248(1):31-40.
32. Ying Q-L, Smith AG (2003) Defined conditions for neural commitment and differentiation. Methods Enzymol 365:327-341.
33. Rhinn M, Dollé P (2012) Retinoic acid signalling during development. Development 139(5):843-858.
34. Mahony S, et al. (2011) Ligand-dependent dynamics of retinoic acid receptor binding during early neurogenesis. Genome Biol 12(1):R2.
35. Moutier E, et al. (2012) Retinoic acid receptors recognize the mouse genome through binding elements with diverse spacing and topology. J Biol Chem 287(31):26328-26341.
36. Martello G, Smith A (2014) The nature of embryonic stem cells. Annu Rev Cell Dev Biol 30(1):647-675.
37. Senner CE, Krueger F, Oxley D, Andrews S, Hemberger M (2012) DNA methylation profiles define stem cell identity and reveal a tight embryonic-extraembryonic lineage boundary. Stem Cells 30(12):2732-2745.
38. Hackett JA, et al. (2013) Synergistic mechanisms of DNA demethylation during transition to ground-state pluripotency. Stem Cell Rep 1(6):518-531.
39. Guo G, et al. (2009) Klf4 reverts developmentally programmed restriction of ground state pluripotency. Development 136(7):1063-1069.
40. Esteban MA, et al. (2010) Vitamin C enhances the generation of mouse and human induced pluripotent stem cells. Cell Stem Cell 6(1):71-79.
41. Schwarz BA, Bar-Nur O, Silva JC, Hochedlinger K (2014) Nanog is dispensable for the generation of induced pluripotent stem cells. Curr Biol 24(3):347-350.
42. Zhao B, et al. (2014) Redox-active quinones induces genome-wide DNA methylation changes by an iron-mediated and Tet-dependent mechanism. Nucleic Acids Res 42(3):1593-1605.
43. Bocker MT, et al. (2012) Hydroxylation of 5-methylcytosine by TET2 maintains the active state of the mammalian HOXA cluster. Nat Commun 3(818):818.
44. Wei S, et al.; van Bennekum AM (2001) Biochemical basis for depressed serum retinol levels in transthyretin-deficient mice. J Biol Chem 276(2):1107-1113.
45. Thurnham DI, Mburu ASW, Mwaniki DL, De Wagt A (2005) Micronutrients in childhood and the influence of subclinical inflammation. Proc Nutr Soc 64(4):502-509.
46. Ko M, et al. (2015) TET proteins and 5-methylcytosine oxidation in hematological cancers. Immunol Rev 263(1):6-21.
47. Hu J, et al. (2009) Long-term efficacy and safety of all-trans retinoic acid/arsenic trioxidebased therapy in newly diagnosed acute promyelocytic leukemia. Proc Natl Acad Sci USA 106(9):3342-3347.
48. Lo-Coco F, et al.; Gruppo Italiano Malattie Ematologiche dell'Adulto; German-Austrian Acute Myeloid Leukemia Study Group; Study Alliance Leukemia (2013) Retinoic acid and arsenic trioxide for acute promyelocytic leukemia. N Engl J Med 369(2):111-121.
49. Shen Y, et al. (2015) Mutations of epigenetic modifier genes as a poor prognostic factor in acute promyelocytic leukemia under treatment with all-trans retinoic acid and arsenic trioxide. EBioMedicine 2(6):563-571.
50. Bachman M, et al. (2014) 5-Hydroxymethylcytosine is a predominantly stable DNA modification. Nat Chem 6(12):1049-1055.
51. Ran FA, et al. (2013) Genome engineering using the CRISPR-Cas9 system. Nat Protoc 8(11):2281-2308.
52. Verschoor MJ, Molot LA (2013) A comparison of three colorimetric methods of ferrous and total reactive iron measurement in freshwaters. Limnol Oceanogr Methods 11(3):113-125.
53. Hu L, et al. (2013) Crystal structure of TET2-DNA complex: Insight into TET-mediated 5mC oxidation. Cell 155(7):1545-1555.
54. Smith AG, Hooper ML (1987) Buffalo rat liver cells produce a diffusible activity which inhibits the differentiation of murine embryonal carcinoma and embryonic stem cells. Dev Biol 121(1):1-9.
55. Hu X, et al. (2014) Tet and TDG mediate DNA demethylation essential for mesenchymalto-epithelial transition in somatic cell reprogramming. Cell Stem Cell 14(4):512-522.