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Mammalian DNA methylation and its roles during the induced re-programming of somatic cells

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  • College of Life Science, Northeast Forestry University, Harbin 150040, China

Received date: 2013-12-30

  Revised date: 2014-02-27

  Online published: 2014-05-25

Abstract

The technology of induced pluripotent stem cell (iPS) provides the possibility to reverse the terminal differentiated cells to pluripotent stem cells, and is therefore of great importance in both the theoretical research of stem cells and regenerative medicine. However, the efficiency of current induced reprogramming methods is extremely low, and the incomplete reprogramming often happens. It has been reported that some epigenetic memory of the somatic cells exists in these incomplete reprogrammed iPS cells, and DNA methylation, as a relative long-term and stable epigenetic modification, is one of the important factors that influence the efficiency of reprogramming and differentiative capacity of iPS cells. Mammalian DNA methylation, which normally appears on the CpG sites, occurs on the fifth carbon atom of the cytosine ring. DNA methylation can modulate the expression of somatic cell specific genes, and pluripotent genes; hence, it plays important roles in the processes of mammalian gene regulation, embryonic development and cell reprogramming. In addi-tion, it has also been found that abnormal DNA methylation may lead to the disorder of genetic imprinting and the inactiva-tion of X chromosome in iPS cells. Therefore, in order to provide a concise guidance of DNA methylation studies in iPS, we mainly review the mechanism, the distribution features of DNA methylation, and its roles in induced reprogramming of somatic cells.

Cite this article

Hongwei Song, Tiezhu An, Shanhua Piao, Chunsheng Wang . Mammalian DNA methylation and its roles during the induced re-programming of somatic cells[J]. Hereditas(Beijing), 2014 , 36(5) : 431 -438 . DOI: 10.3724/SP.J.1005.2014.0431

References

[1] Cantone I, Fisher AG. Epigenetic programming and repro-gramming during development. Nat Struct Mol Biol, 2013, 20(3): 282–289. <\p>

[2] Apostolou E, Hochedlinger K. Chromatin dynamics during cellular reprogramming. Nature, 2013, 502(7472): 462– 471. <\p>

[3] Papp B, Plath K. Epigenetics of reprogramming to induced pluripotency. Cell, 2013, 152(6): 1324–1343. <\p>

[4] Waddington CH. The Strategy of the Genes. London: George Allen & Unwin, 1957. <\p>

[5] Hochedlinger K, Plath K. Epigenetic reprogramming and induced pluripotency. Development, 2009, 136(4): 509–523. <\p>

[6] Watanabe A, Yamada Y, Yamanaka S. Epigenetic regula-tion in pluripotent stem cells: a key to breaking the epi-genetic barrier. Philos Trans R Soc Lond B Biol Sci, 2013, 368(1609): 20120292, doi: 10.1098/rstb.2012.0292. <\p>

[7] Simonsson S, Gurdon J. DNA demethylation is necessary for the epigenetic reprogramming of somatic cell nuclei. Nat Cell Biol, 2004, 6(10): 984–990. <\p>

[8] Koche RP, Smith ZD, Adli M, Gu H, Ku M, Gnirke A, Bernstein BE, Meissner A. Reprogramming factor expres-sion initiates widespread targeted chromatin remodeling. Cell Stem Cell, 2011, 8(1): 96–105. <\p>

[9] Sulewska A, Niklinska W, Kozlowski M, Minarowski L, Naumnik W, Niklinski J, Dabrowska K, Chyczewski L. DNA methylation in states of cell physiology and pathol-ogy. Folia Histochem Cytobiol, 2007, 45(3): 149–158. <\p>

[10] Bestor TH, Bourc'his D. Transposon silencing and imprint establishment in mammalian germ cells. Cold Spring Harb Symp Quant Biol, 2004, 69: 381–387. <\p>

[11] Jaenisch R, Bird A. Epigenetic regulation of gene expres-sion: how the genome integrates intrinsic and environ-mental signals. Nat Genet, 2003, 33(Suppl.): 245–254. <\p>

[12] Goll MG, Bestor TH. Eukaryotic cytosine methyltransferases. Annu Rev Biochem, 2005, 74(1): 481–514. <\p>

[13] Bostick M, Kim JK, Esteve PO, Clark A, Pradhan S, Jacobsen SE. UHRF1 plays a role in maintaining DNA methylation in mammalian cells. Science, 2007, 317(5845): 1760–1764. <\p>

[14] Li E, Bestor TH, Jaenisch R. Targeted mutation of the DNA methyltransferase gene results in embryonic lethality. Cell, 1992, 69(6): 915–926. <\p>

[15] Koh KP, Rao A. DNA methylation and methylcytosine oxidation in cell fate decisions. Curr Opin Cell Biol, 2013, 25(2): 152–161. <\p>

[16] Okano M, Bell DW, Haber DA, Li E. DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development. Cell, 1999, 99(3): 247–257. <\p>

[17] Chen ZX, Mann JR, Hsieh CL, Riggs AD, Chedin F. Physical and functional interactions between the human DNMT3L protein and members of the de novo methyltransferase family. J Cell Biochem, 2005, 95(5): 902–917. <\p>

[18] Ooi SK, Qiu C, Bernstein E, Li K, Jia D, Yang Z, Erd-jument-Bromage H, Tempst P, Lin SP, Allis CD, Cheng X, Bestor TH. DNMT3L connects unmethylated lysine 4 of histone H3 to de novo methylation of DNA. Nature, 2007, 448(7154): 714–717. <\p>

[19] 许力凡, 张记, 田志强, 吴玉章. 表观遗传学与肿瘤干细胞. 遗传, 2013, 35(9): 1049–1057. <\p>

[20] Tsai HC, Li HL, Van Neste L, Cai Y, Robert C, Rassool FV, Shin JJ, Harbom KM, Beaty R, Pappou E, Harris J, Yen RW, Ahuja N, Brock MV, Stearns V, Feller-Kopman D, Yarmus LB, Lin YC, Welm AL, Issa JP, Minn I, Matsui W, Jang YY, Sharkis SJ, Baylin SB, Zahnow CA. Transient low doses of DNA-demethylating agents exert durable an-titumor effects on hematological and epithelial tumor cells. Cancer Cell, 2012, 21(3): 430–446. <\p>

[21] Feng S, Jacobsen SE, Reik W. Epigenetic reprogramming in plant and animal development. Science, 2010, 330(6004): 622–627. <\p>

[22] Ko

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