Epigenetic regulation of smooth muscle cell plasticity

Biochimica et Biophysica Acta - Gene Regulatory Mechanisms

Volumn 1849, Issue 4, 2015, Pages 448-453

  Liu, Renjing ^a,b   Leslie, Kristen L ^c   Martin, Kathleen A ^c  

^a CENTENARY INSTITUTE   (Australia)

^b UNIVERSITY OF SYDNEY   (Australia)

^c YALE UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Chromatin; DNA methylation; Epigenetics; Smooth muscle phenotype; TET2; Transcription

Indexed keywords

DNA; DNA METHYLTRANSFERASE; HISTONE DEACETYLASE 2; HISTONE DEACETYLASE 4; HISTONE DEACETYLASE 5; INTERSTITIAL COLLAGENASE; KRUPPEL LIKE FACTOR 4; MYOSIN HEAVY CHAIN; TET2 PROTEIN; UNCLASSIFIED DRUG; DNA BINDING PROTEIN; ONCOPROTEIN; TET2 PROTEIN, HUMAN;

ATHEROSCLEROSIS; CEREBROVASCULAR ACCIDENT; DNA METHYLATION; EPIGENETICS; GENETIC TRANSCRIPTION; HISTONE MODIFICATION; ISCHEMIC HEART DISEASE; NONHUMAN; PLASTICITY; PRIORITY JOURNAL; REVIEW; SMOOTH MUSCLE FIBER; ADULT; ANIMAL; CELL DEDIFFERENTIATION; CELL DIFFERENTIATION; DISEASES; GENETIC EPIGENESIS; GENETICS; HEALTH; HUMAN; PHYSIOLOGY;

ADULT; ANIMALS; CELL DEDIFFERENTIATION; CELL DIFFERENTIATION; DISEASE; DNA METHYLATION; DNA-BINDING PROTEINS; EPIGENESIS, GENETIC; HEALTH; HUMANS; MYOCYTES, SMOOTH MUSCLE; PROTO-ONCOGENE PROTEINS;

EID: 84924227763     PISSN: 18749399     EISSN: 18764320     Source Type: Journal    
DOI: 10.1016/j.bbagrm.2014.06.004     Document Type: Review

References (85)

1. Owens G.K. Regulation of differentiation of vascular smooth muscle cells. Physiol. Rev. 1995, 75:487-517.
2. Rzucidlo E.M., Martin K.A., Powell R.J. Regulation of vascular smooth muscle cell differentiation. J. Vasc. Surg. 2007, 45:A25-A32. (Suppl. A).
3. Sobue K., Hayashi K., Nishida W. Expressional regulation of smooth muscle cell-specific genes in association with phenotypic modulation. Mol. Cell. Biochem. 1999, 190:105-118.
4. Sobue K., Hayashi K., Nishida W. Molecular mechanism of phenotypic modulation of smooth muscle cells. Horm. Res. 1998, 50(Suppl. 2):15-24.
5. Gomez D., Owens G.K. Smooth muscle cell phenotypic switching in atherosclerosis. Cardiovasc. Res. 2012, 95:156-164.
6. Gomez D., Shankman L.S., Nguyen A.T., Owens G.K. Detection of histone modifications at specific gene loci in single cells in histological sections. Nat. Methods 2013, 10:171-177.
7. Nguyen A.T., Gomez D., Bell R.D., Campbell J.H., Clowes A.W., Gabbiani G., Giachelli C.M., Parmacek M.S., Raines E.W., Rusch N.J., Speer M.Y., Sturek M., Thyberg J., Towler D.A., Weiser-Evans M.C., Yan C., Miano J.M., Owens G.K. Smooth muscle cell plasticity: fact or fiction?. Circ. Res. 2013, 112:17-22.
8. Rong J.X., Shapiro M., Trogan E., Fisher E.A. Transdifferentiation of mouse aortic smooth muscle cells to a macrophage-like state after cholesterol loading. Proc. Natl. Acad. Sci. U. S. A. 2003, 100:13531-13536.
9. Clowes A.W., Reidy M.A., Clowes M.M. Mechanisms of stenosis after arterial injury. Lab. Invest. 1983, 49:208-215.
10. Chaabane C., Otsuka F., Virmani R., Bochaton-Piallat M.L. Biological responses in stented arteries. Cardiovasc. Res. 2013, 99:353-363.
11. Norman P.E., Curci J.A. Understanding the effects of tobacco smoke on the pathogenesis of aortic aneurysm. Arterioscler. Thromb. Vasc. Biol. 2013, 33:1473-1477.
12. Ailawadi G., Moehle C.W., Pei H., Walton S.P., Yang Z., Kron I.L., Lau C.L., Owens G.K. Smooth muscle phenotypic modulation is an early event in aortic aneurysms. J. Thorac. Cardiovasc. Surg. 2009, 138:1392-1399.
13. Libby P., Ridker P.M., Hansson G.K., A.Leducq Transatlantic Network on Inflammation in atherosclerosis: from pathophysiology to practice. J. Am. Coll. Cardiol. 2009, 54:2129-2138.
14. Wagner R.J., Martin K.A., Powell R.J., Rzucidlo E.M. Lovastatin induces VSMC differentiation through inhibition of Rheb and mTOR. Am. J. Physiol. Cell Physiol. 2010, 299:C119-C127.
15. Seedial S.M., Ghosh S., Saunders R.S., Suwanabol P.A., Shi X., Liu B., Kent K.C. Local drug delivery to prevent restenosis. J. Vasc. Surg. 2013, 57:1403-1414.
16. Martin K.A., Rzucidlo E.M., Merenick B.L., Fingar D.C., Brown D.J., Wagner R.J., Powell R.J. The mTOR/p70 S6K1 pathway regulates vascular smooth muscle cell differentiation. Am. J. Physiol. Cell Physiol. 2004, 286:C507-C517.
17. Martin K.A., Merenick B.L., Ding M., Fetalvero K.M., Rzucidlo E.M., Kozul C.D., Brown D.J., Chiu H.Y., Shyu M., Drapeau B.L., Wagner R.J., Powell R.J. Rapamycin promotes vascular smooth muscle cell differentiation through insulin receptor substrate-1/phosphatidylinositol 3-kinase/Akt2 feedback signaling. J. Biol. Chem. 2007, 282:36112-36120.
18. Yi T., Cuchara L., Wang Y., Koh K.P., Ranjbaran H., Tellides G., Pober J.S., Lorber M.I. Human allograft arterial injury is ameliorated by sirolimus and cyclosporine and correlates with suppression of interferon-gamma. Transplantation 2006, 81:559-566.
19. Wang Y., Bai Y., Qin L., Zhang P., Yi T., Teesdale S.A., Zhao L., Pober J.S., Tellides G. Interferon-gamma induces human vascular smooth muscle cell proliferation and intimal expansion by phosphatidylinositol 3-kinase dependent mammalian target of rapamycin raptor complex 1 activation. Circ. Res. 2007, 101:560-569.
20. Miano J.M. Serum response factor: toggling between disparate programs of gene expression. J. Mol. Cell. Cardiol. 2003, 35:577-593.
21. Chen J., Kitchen C.M., Streb J.W., Miano J.M. Myocardin: a component of a molecular switch for smooth muscle differentiation. J. Mol. Cell. Cardiol. 2002, 34:1345-1356.
22. Long X., Bell R.D., Gerthoffer W.T., Zlokovic B.V., Miano J.M. Myocardin is sufficient for a smooth muscle-like contractile phenotype. Arterioscler. Thromb. Vasc. Biol. 2008, 28:1505-1510.
23. Liu Y., Sinha S., McDonald O.G., Shang Y., Hoofnagle M.H., Owens G.K. Kruppel-like factor 4 abrogates myocardin-induced activation of smooth muscle gene expression. J. Biol. Chem. 2005, 280:9719-9727.
24. Liu Z.P., Wang Z., Yanagisawa H., Olson E.N. Phenotypic modulation of smooth muscle cells through interaction of Foxo4 and myocardin. Dev. Cell 2005, 9:261-270.
25. Xin M., Small E.M., Sutherland L.B., Qi X., McAnally J., Plato C.F., Richardson J.A., Bassel-Duby R., Olson E.N. MicroRNAs miR-143 and miR-145 modulate cytoskeletal dynamics and responsiveness of smooth muscle cells to injury. Genes Dev. 2009, 23:2166-2178.
26. Cordes K.R., Sheehy N.T., White M.P., Berry E.C., Morton S.U., Muth A.N., Lee T.H., Miano J.M., Ivey K.N., Srivastava D. miR-145 and miR-143 regulate smooth muscle cell fate and plasticity. Nature 2009, 460:705-710.
27. Cheng Y., Liu X., Yang J., Lin Y., Xu D.Z., Lu Q., Deitch E.A., Huo Y., Delphin E.S., Zhang C. MicroRNA-145, a novel smooth muscle cell phenotypic marker and modulator, controls vascular neointimal lesion formation. Circ. Res. 2009, 105:158-166.
28. Jaenisch R., Bird A. Epigenetic regulation of gene expression: how the genome integrates intrinsic and environmental signals. Nat. Genet. 2003, 33:245-254. (Suppl.).
29. Suto R.K., Clarkson M.J., Tremethick D.J., Luger K. Crystal structure of a nucleosome core particle containing the variant histone H2A.Z. Nat. Struct. Mol. Biol. 2000, 7:1121-1124.
30. Cheung P., Allis C.D., Sassone-Corsi P. Signaling to chromatin through histone modifications. Cell 2000, 103:263-271.
31. Alexander M.R., Owens G.K. Epigenetic control of smooth muscle cell differentiation and phenotypic switching in vascular development and disease. Annu. Rev. Physiol. 2012, 74:13-40.
32. Manabe I., Owens G.K. Recruitment of serum response factor and hyperacetylation of histones at smooth muscle-specific regulatory regions during differentiation of a novel P19-derived in vitro smooth muscle differentiation system. Circ. Res. 2001, 88:1127-1134.
33. Qiu P., Li L. Histone acetylation and recruitment of serum responsive factor and CREB-binding protein onto SM22 promoter during SM22 gene expression. Circ. Res. 2002, 90:858-865.
34. Qiu P., Ritchie R.P., Gong X.Q., Hamamori Y., Li L. Dynamic changes in chromatin acetylation and the expression of histone acetyltransferases and histone deacetylases regulate the SM22α transcription in response to Smad3-mediated TGFβ1 signaling. Biochem. Biophys. Res. Commun. 2006, 348:351-358.
35. Cao D., Wang Z., Zhang C.-L., Oh J., Xing W., Li S., Richardson J.A., Wang D.-Z., Olson E.N. Modulation of smooth muscle gene expression by association of histone acetyltransferases and deacetylases with myocardin. Mol. Cell. Biol. 2005, 25:364-376.
36. Yoshida T., Gan Q., Shang Y., Owens G.K. Platelet-derived growth factor-BB represses smooth muscle cell marker genes via changes in binding of MKL factors and histone deacetylases to their promoters. Am. J. Physiol. Cell Physiol. 2007, 292:C886-C895.
37. McDonald O.G., Wamhoff B.R., Hoofnagle M.H., Owens G.K. Control of SRF binding to CArG box chromatin regulates smooth muscle gene expression in vivo. J. Clin. Invest. 2006, 116:36-48.
38. Gan Q., Thiébaud P., Thézé N., Jin L., Xu G., Grant P., Owens G.K. WD repeat-containing protein 5, a ubiquitously expressed histone methyltransferase adaptor protein, regulates smooth muscle cell-selective gene activation through interaction with pituitary homeobox 2. J. Biol. Chem. 2011, 286:21853-21864.
39. Chen S., Lechleider R.J. Transforming growth factor-β-induced differentiation of smooth muscle from a neural crest stem cell line. Circ. Res. 2004, 94:1195-1202.
40. Sinha S., Hoofnagle M.H., Kingston P.A., McCanna M.E., Owens G.K. Transforming growth factor-beta1 signaling contributes to development of smooth muscle cells from embryonic stem cells. Am. J. Physiol. Cell Physiol. 2004, 287:C1560-C1568.
41. Thomas J.A., Deaton R.A., Hastings N.E., Shang Y., Moehle C.W., Eriksson U., Topouzis S., Wamhoff B.R., Blackman B.R., Owens G.K. PDGF-DD, a novel mediator of smooth muscle cell phenotypic modulation, is upregulated in endothelial cells exposed to atherosclerosis-prone flow patterns. Am. J. Physiol. Heart Circ. Physiol. 2009, 296:H442-H452.
42. Starke R.M., Ali M.S., Jabbour P.M., Tjoumakaris S.I., Gonzalez F., Hasan D.M., Rosenwasser R.H., Owens G.K., Koch W.J., Dumont A.S. Cigarette smoke modulates vascular smooth muscle phenotype: implications for carotid and cerebrovascular disease. PLoS One 2013, 8:e71954.
43. Watson A.D., Leitinger N., Navab M., Faull K.F., Hörkkö S., Witztum J.L., Palinski W., Schwenke D., Salomon R.G., Sha W., Subbanagounder G., Fogelman A.M., Berliner J.A. Structural identification by mass spectrometry of oxidized phospholipids in minimally oxidized low density lipoprotein that induce monocyte/endothelial interactions and evidence for their presence in vivo. J. Biol. Chem. 1997, 272:13597-13607.
44. Liao F., Berliner J.A., Mehrabian M., Navab M., Demer L.L., Lusis A.J., Fogelman A.M. Minimally modified low density lipoprotein is biologically active in vivo in mice. J. Clin. Invest. 1991, 87:2253-2257.
45. Yoshida T., Gan Q., Owens G.K. Krüppel-like factor 4, Elk-1, and histone deacetylases cooperatively suppress smooth muscle cell differentiation markers in response to oxidized phospholipids. Am. J. Physiol. Cell Physiol. 2008, 295:C1175-C1182.
46. Salmon M., Gomez D., Greene E., Shankman L., Owens G.K. Cooperative binding of KLF4, pELK-1, and HDAC2 to a G/C repressor element in the SM22α promoter mediates transcriptional silencing during SMC phenotypic switching in vivo. Circ. Res. 2012, 111:685-696.
47. Weng X., Cheng X., Wu X., Xu H., Fang M., Xu Y. Sin3B mediates collagen type I gene repression by interferon gamma in vascular smooth muscle cells. Biochem. Biophys. Res. Commun. 2014, 447:263-270.
48. Usui T., Morita T., Okada M., Yamawaki H. Histone deacetylase 4 controls neointimal hyperplasia via stimulating proliferation and migration of vascular smooth muscle cells. Hypertension 2014, 63:397-403.
49. Kee H.J., Kwon J.-S., Shin S., Ahn Y., Jeong M.H., Kook H. Trichostatin A prevents neointimal hyperplasia via activation of Krüppel like factor 4. Vasc. Pharmacol. 2011, 55:127-134.
50. Jones P.A., Takai D. The role of DNA methylation in mammalian epigenetics. Science 2001, 293:1068-1070.
51. Bestor T.H. The DNA methyltransferases of mammals. Hum. Mol. Genet. 2000, 9:2395-2402.
52. Hiltunen M.O., Turunen M.P., Hakkinen T.P., Rutanen J., Hedman M., Makinen K., Turunen A.M., Aalto-Setala K., Yla-Herttuala S. DNA hypomethylation and methyltransferase expression in atherosclerotic lesions. Vasc. Med. 2002, 7:5-11.
53. Connelly J.J., Cherepanova O.A., Doss J.F., Karaoli T., Lillard T.S., Markunas C.A., Nelson S., Wang T., Ellis P.D., Langford C.F., Haynes C., Seo D.M., Goldschmidt-Clermont P.J., Shah S.H., Kraus W.E., Hauser E.R., Gregory S.G. Epigenetic regulation of COL15A1 in smooth muscle cell replicative aging and atherosclerosis. Hum. Mol. Genet. 2013, 22:5107-5120.
54. Laukkanen M.O., Mannermaa S., Hiltunen M.O., Aittomaki S., Airenne K., Janne J., Yla-Herttuala S. Local hypomethylation in atherosclerosis found in rabbit ec-sod gene. Arterioscler. Thromb. Vasc. Biol. 1999, 19:2171-2178.
55. Nakamura Y., Suzuki T., Miki Y., Tazawa C., Senzaki K., Moriya T., Saito H., Ishibashi T., Takahashi S., Yamada S., Sasano H. Estrogen receptors in atherosclerotic human aorta: inhibition of human vascular smooth muscle cell proliferation by estrogens. Mol. Cell. Endocrinol. 2004, 219:17-26.
56. Ying A.K., Hassanain H.H., Roos C.M., Smiraglia D.J., Issa J.J., Michler R.E., Caligiuri M., Plass C., Goldschmidt-Clermont P.J. Methylation of the estrogen receptor-alpha gene promoter is selectively increased in proliferating human aortic smooth muscle cells. Cardiovasc. Res. 2000, 46:172-179.
57. Wang Y.S., Chou W.W., Chen K.C., Cheng H.Y., Lin R.T., Juo S.H. MicroRNA-152 mediates DNMT1-regulated DNA methylation in the estrogen receptor alpha gene. PLoS One 2012, 7:e30635.
58. Azechi T., Sato F., Sudo R., Wachi H. 5-Aza-2 -deoxycytidine, a DNA methyltransferase inhibitor, facilitates the inorganic phosphorus-induced mineralization of vascular smooth muscle cells. J. Atheroscler. Thromb. 2014, 21(5):463-476.
59. Raines E.W. The extracellular matrix can regulate vascular cell migration, proliferation, and survival: relationships to vascular disease. Int. J. Exp. Pathol. 2000, 81:173-182.
60. Hodges S.J., Yoo J.J., Mishra N., Atala A. The effect of epigenetic therapy on congenital neurogenic bladders-a pilot study. Urology 2010, 75:868-872.
61. Ning Y., Huang H., Dong Y., Sun Q., Zhang W., Xu W., Li Q. 5-Aza-2'-deoxycytidine inhibited PDGF-induced rat airway smooth muscle cell phenotypic switching. Arch. Toxicol. 2013, 87:871-881.
62. Jiang J.X., Aitken K.J., Sotiropolous C., Kirwan T., Panchal T., Zhang N., Pu S., Wodak S., Tolg C., Bagli D.J. Phenotypic switching induced by damaged matrix is associated with DNA methyltransferase 3A (DNMT3A) activity and nuclear localization in smooth muscle cells (SMC). PLoS One 2013, 8:e69089.
63. Mousa A.A., Cappello R.E., Estrada-Gutierrez G., Shukla J., Romero R., Strauss J.F., Walsh S.W. Preeclampsia is associated with alterations in DNA methylation of genes involved in collagen metabolism. Am. J. Pathol. 2012, 181:1455-1463.
64. Tahiliani M., Koh K.P., Shen Y., Pastor W.A., Bandukwala H., Brudno Y., Agarwal S., Iyer L.M., Liu D.R., Aravind L., Rao A. Conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA by MLL partner TET1. Science 2009, 324:930-935.
65. Ito S., D'Alessio A.C., Taranova O.V., Hong K., Sowers L.C., Zhang Y. Role of Tet proteins in 5mC to 5hmC conversion, ES-cell self-renewal and inner cell mass specification. Nature 2010, 466:1129-1133.
66. Kriaucionis S., Heintz N. The nuclear DNA base 5-hydroxymethylcytosine is present in Purkinje neurons and the brain. Science 2009, 324:929-930.
67. He Y.F., Li B.Z., Li Z., Liu P., Wang Y., Tang Q., Ding J., Jia Y., Chen Z., Li L., Sun Y., Li X., Dai Q., Song C.X., Zhang K., He C., Xu G.L. Tet-mediated formation of 5-carboxylcytosine and its excision by TDG in mammalian DNA. Science 2011, 333:1303-1307.
68. Tan L., Shi Y.G. Tet family proteins and 5-hydroxymethylcytosine in development and disease. Development 2012, 139:1895-1902.
69. Shen L., Zhang Y. 5-Hydroxymethylcytosine: generation, fate, and genomic distribution. Curr. Opin. Cell Biol. 2013, 25:289-296.
70. Lorsbach R.B., Moore J., Mathew S., Raimondi S.C., Mukatira S.T., Downing J.R. TET1, a member of a novel protein family, is fused to MLL in acute myeloid leukemia containing the t(10;11)(q22;q23). Leukemia 2003, 17:637-641.
71. Wu H., D'Alessio A.C., Ito S., Xia K., Wang Z., Cui K., Zhao K., Sun Y.E., Zhang Y. Dual functions of Tet1 in transcriptional regulation in mouse embryonic stem cells. Nature 2011, 473:389-393.
72. Koh K.P., Yabuuchi A., Rao S., Huang Y., Cunniff K., Nardone J., Laiho A., Tahiliani M., Sommer C.A., Mostoslavsky G., Lahesmaa R., Orkin S.H., Rodig S.J., Daley G.Q., Rao A. Tet1 and Tet2 regulate 5-hydroxymethylcytosine production and cell lineage specification in mouse embryonic stem cells. Cell Stem Cell 2011, 8:200-213.
73. Delhommeau F., Dupont S., Della Valle V., James C., Trannoy S., Masse A., Kosmider O., Le Couedic J.P., Robert F., Alberdi A., Lecluse Y., Plo I., Dreyfus F.J., Marzac C., Casadevall N., Lacombe C., Romana S.P., Dessen P., Soulier J., Viguie F., Fontenay M., Vainchenker W., Bernard O.A. Mutation in TET2 in myeloid cancers. N. Engl. J. Med. 2009, 360:2289-2301.
74. Moran-Crusio K., Reavie L., Shih A., Abdel-Wahab O., Ndiaye-Lobry D., Lobry C., Figueroa M.E., Vasanthakumar A., Patel J., Zhao X., Perna F., Pandey S., Madzo J., Song C., Dai Q., He C., Ibrahim S., Beran M., Zavadil J., Nimer S.D., Melnick A., Godley L.A., Aifantis I., Levine R.L. Tet2 loss leads to increased hematopoietic stem cell self-renewal and myeloid transformation. Cancer Cell 2011, 20:11-24.
75. Ko M., Huang Y., Jankowska A.M., Pape U.J., Tahiliani M., Bandukwala H.S., An J., Lamperti E.D., Koh K.P., Ganetzky R., Liu X.S., Aravind L., Agarwal S., Maciejewski J.P., Rao A. Impaired hydroxylation of 5-methylcytosine in myeloid cancers with mutant TET2. Nature 2010, 468:839-843.
76. Gu T.P., Guo F., Yang H., Wu H.P., Xu G.F., Liu W., Xie Z.G., Shi L., He X., Jin S.G., Iqbal K., Shi Y.G., Deng Z., Szabo P.E., Pfeifer G.P., Li J., Xu G.L. The role of Tet3 DNA dioxygenase in epigenetic reprogramming by oocytes. Nature 2011, 477:606-610.
77. Liu R., Jin Y., Tang W.H., Qin L., Zhang X., Tellides G., Hwa J., Yu J., Martin K.A. Ten-eleven translocation-2 (TET2) is a master regulator of smooth muscle cell plasticity. Circulation 2013, 128:2047-2057.
78. Williams K., Christensen J., Pedersen M.T., Johansen J.V., Cloos P.A., Rappsilber J., Helin K. TET1 and hydroxymethylcytosine in transcription and DNA methylation fidelity. Nature 2011, 473:343-348.
79. Wu H., D'Alessio A.C., Ito S., Wang Z., Cui K., Zhao K., Sun Y.E., Zhang Y. Genome-wide analysis of 5-hydroxymethylcytosine distribution reveals its dual function in transcriptional regulation in mouse embryonic stem cells. Genes Dev. 2011, 25:679-684.
80. Ficz G., Branco M.R., Seisenberger S., Santos F., Krueger F., Hore T.A., Marques C.J., Andrews S., Reik W. Dynamic regulation of 5-hydroxymethylcytosine in mouse ES cells and during differentiation. Nature 2011, 473:398-402.
81. Pastor W.A., Pape U.J., Huang Y., Henderson H.R., Lister R., Ko M., McLoughlin E.M., Brudno Y., Mahapatra S., Kapranov P., Tahiliani M., Daley G.Q., Liu X.S., Ecker J.R., Milos P.M., Agarwal S., Rao A. Genome-wide mapping of 5-hydroxymethylcytosine in embryonic stem cells. Nature 2011, 473:394-397.
82. Klug M., Schmidhofer S., Gebhard C., Andreesen R., Rehli M. 5-Hydroxymethylcytosine is an essential intermediate of active DNA demethylation processes in primary human monocytes. Genome Biol. 2013, 14:R46.
83. Lian C.G., Xu Y., Ceol C., Wu F., Larson A., Dresser K., Xu W., Tan L., Hu Y., Zhan Q., Lee C.W., Hu D., Lian B.Q., Kleffel S., Yang Y., Neiswender J., Khorasani A.J., Fang R., Lezcano C., Duncan L.M., Scolyer R.A., Thompson J.F., Kakavand H., Houvras Y., Zon L.I., Mihm M.C., Kaiser U.B., Schatton T., Woda B.A., Murphy G.F., Shi Y.G. Loss of 5-hydroxymethylcytosine is an epigenetic hallmark of melanoma. Cell 2012, 150:1135-1146.
84. Kallin E.M., Rodriguez-Ubreva J., Christensen J., Cimmino L., Aifantis I., Helin K., Ballestar E., Graf T. Tet2 facilitates the derepression of myeloid target genes during CEBPalpha-induced transdifferentiation of pre-B cells. Mol. Cell 2012, 48:266-276.
85. Doege C.A., Inoue K., Yamashita T., Rhee D.B., Travis S., Fujita R., Guarnieri P., Bhagat G., Vanti W.B., Shih A., Levine R.L., Nik S., Chen E.I., Abeliovich A. Early-stage epigenetic modification during somatic cell reprogramming by Parp1 and Tet2. Nature 2012, 488:652-655.