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Cellular and Molecular Life Sciences

, Volume 71, Issue 6, pp 1017–1032 | Cite as

Epigenetic choreography of stem cells: the DNA demethylation episode of development

  • Swayamsiddha Kar
  • Sabnam Parbin
  • Moonmoon Deb
  • Arunima Shilpi
  • Dipta Sengupta
  • Sandip Kumar Rath
  • Madhumita Rakshit
  • Aditi Patra
  • Samir Kumar PatraEmail author
Review

Abstract

Reversible DNA methylation is a fundamental epigenetic manipulator of the genomic information in eukaryotes. DNA demethylation plays a very significant role during embryonic development and stands out for its contribution in molecular reconfiguration during cellular differentiation for determining stem cell fate. DNA demethylation arbitrated extensive make-over of the genome via reprogramming in the early embryo results in stem cell plasticity followed by commitment to the principal cell lineages. This article attempts to highlight the sequential phases and hierarchical mode of DNA demethylation events during enactment of the molecular strategy for developmental transition. A comprehensive knowledge regarding the pattern of DNA demethylation during embryogenesis and organogenesis and study of the related lacunae will offer exciting avenues for future biomedical research and stem cell-based regenerative therapy.

Keywords

DNA demethylation Stem cell Epigenetics Development 

Abbreviations

5meC

5 Methylcytosine

ABL1

c-abl oncogene 1

AID

Activation-induced deaminase

AML

Acute myelogenous leukemia

APOBEC

Apolipoprotein B mRNA editing enzyme catalytic polypeptide

ARL4C

ADP-ribosylation factor-like 4C

ASCL1

Achaete-scute complex homologue 1

AZA

5-Aza-2′-deoxycytidine

BDNF

Brain-derived neurotrophic factor

BER

Base excision repair glycosylases

BGLAP

Bone gamma-carboxyglutamate (Gla) protein

BMP2

Bone morphogenetic protein 2

BMP4

Bone morphogenetic protein 4

CALC-α

Calcitonin-related polypeptide alpha

CDKN2B

Cyclin-dependent kinase inhibitor 2B

CEBP-α

CCAAT/enhancer-binding protein alpha

CHAD

Chondroadherin

CHK2

Checkpoint kinase 2

CHM1

Chondromodulin-I

CLPs

Common lymphoid progenitors

CML

Chronic myelomonocytic leukemia

CMPs

Common myeloid progenitors

CNS

Central nervous system

CNTF

Ciliary neurotrophic factor

Col10a1

α1(X) collagen

Col2a1

α1 (II) collagen

CT1

Cardiotrophin-1

CTLA4

Cytotoxic T-lymphocyte-associated protein

CTNNA1

Catenin (cadherin-associated protein), Alpha 1

CXCR2

Chemokine (C-X-C Motif) receptor 2

DACH1

Dachshund homolog 1

DAZL

Deleted in azoospermia-like

DC-SIGN

Dendritic cell-specific ICAM-3 grabbing non-integrin

DMD

Duchenne muscular dystrophy

DNMT1

DNA methyltransferase 1

E-CAD

E-cadherin

EGCs

Embryonic germ cells

ELF5

E-74-like factor 5

ELP3

Elongator complex protein 3

ESCs

Embryonic stem cells

FABP4

Fatty acid-binding protein 4

FGF2

Fibroblast growth factors

FGFR3

Fibroblast growth factor receptor-3

GADD45A

Growth arrest and DNA damage-inducible protein 45α

GCNT2

Glucosaminyl (N-acetyl) transferase 2; I-branching enzyme (I Blood Group)

GFAP

Glial fibrillary acidic protein

GLUT4

Glucose transporter type 4

GMPs

Granulocyte/macrophage progenitors

GP6/GP VI

Platelet glycoprotein 6/VI

HSCs

Hematopoietic stem cells

ICM

Inner cell mass

IFN-γ

Interferon-gamma

IL-13

Interleukin 13

IL-17

Interleukin 17A

IL-1β

Interleukin-1β

IL-2

Interleukin 2

IL-4

Interleukin 4

IL-6

Interleukin-6

iPSCs

Induced pluripotent stem cells

iTreg

Induced regulatory T

JAK–STAT

Janus Kinase-signal transducer and activator of transcription

JDP2

Jun dimerization protein 2

JMML

Juvenile myelomonocytic leukemia

LAG3

Lymphocyte-activation gene 3

LEP

Leptin

LIF

Leukemia inhibitory factor

LPL

Lipoprotein lipase

MATH3

Mammalian atonal homologue 3

MBD2b

Methyl-binding domain protein 2b

MBD4

Methyl-binding domain protein 4

MDS

Myelodysplastic syndromes

MEPs

Megakaryocyte/erythroid progenitors

MGMT

O6-methylguanine-DNA methyltransferase

MHC II

Major histocompatibility complex, class II

MPO

Myeloperoxidase

MRFs

Myogenic regulatory factors

MSCs

Mesenchymal stem cells

MYF-5

Myogenic factor 5

MYOD

Myogenic differentiation

MYOG

Myogenin

NEUROG2

Neurogenin 2

NK

Natural killer

NKG2A

NK cell receptor A, also known as KLRC1 (C-type lectin-like inhibitory receptor)

NR4A2

Nuclear receptor subfamily 4, group A, member 2

NRG

Neuregulins

NSCs

Neural stem cells

OC

Osteocalcin

OCT4

Octamer-binding transcription factor 4

OPCs

Oligodendrocyte progenitor cells

OPN

Osteopontin

OSX

Osterix

PAX3

Paired box 3

PAX5

Paired box protein 5

PCD1

Programmed cell death 1

PDGF

Platelet-derived growth factors

PGCs

Primordial germ cells

PI-PLC beta1

Phosphoinositide-phospholipase C beta1

PPARγ and PPARγ2

Peroxisome proliferator-activated receptor-gamma

PRF1

Perforin 1

PU1

Purine box factor 1

RAR-β

Retinoic acid receptor beta

ROR-γt

Retinoic-acid-receptor-related orphan receptor-γt, or RORC

RUNX1

Runt-related transcription factor 1

RUNX2

Runt-related transcription factor 2

SOX2

SRY box-containing factor 2

SOX9

SRY (sex determining region Y) box 9

SYCP3

Synaptonemal complex protein 3

TBX21

Transcription factor T-Box 21, or T-bet

TDG

Thymine DNA glycosylase

TE

Trophectoderm

TET

Ten-eleven translocation proteins

TH

T helper

TIM3

T-cell immunoglobulin mucin 3

TNK

T cell and natural killer cell

VASN

Vasorin

WT1

Wilms tumor 1

Notes

Acknowledgments

S. Kar, A. Shilpi, D. Sengupta, M. Deb, and S. K. Rath are thankful to NIT-Rourkela for granting them fellowships under the Institute Research Scheme. S. Parbin is thankful to DST, government of India for an INSPIRE fellowship. M. Rakshit is thankful to NIT-Rourkela for granting her a postdoctoral research associate position with institute fellowship. We thankfully acknowledge the suggestions and critics of the anonymous reviewer on the original manuscript.

Conflict of interest

The authors declare that they do not have any conflict of interest to report.

References

  1. 1.
    Vincent A, Van Seuningen I (2009) Epigenetics, stem cells and epithelial cell fate. Differentiation 78(2–3):99–107PubMedCrossRefGoogle Scholar
  2. 2.
    De Carvalho DD, You JS, Jones PA (2010) DNA methylation and cellular reprogramming. Trends Cell Biol 20(10):609–617PubMedCentralPubMedCrossRefGoogle Scholar
  3. 3.
    Collas P (2009) Epigenetic states in stem cells. Biochem Biophys Acta 1790(9):900–905PubMedCrossRefGoogle Scholar
  4. 4.
    Zhao X, Ruan Y, Wei CL (2008) Tackling the epigenome in the pluripotent stem cells. J Genet Genomics 35(7):403–412PubMedCrossRefGoogle Scholar
  5. 5.
    Berdasco M, Esteller M (2011) DNA methylation in stem cell renewal and multipotency. Stem Cell Res Ther 2(5):42–51PubMedCentralPubMedCrossRefGoogle Scholar
  6. 6.
    Szutorisz H, Dillon N (2005) The epigenetic basis for embryonic stem cell pluripotency. BioEssays 27(12):1286–1293PubMedCrossRefGoogle Scholar
  7. 7.
    Altun G, Loring JF, Laurent LC (2010) DNA methylation in embryonic stem cells. J Cell Biochem 109(1):1–6PubMedCentralPubMedGoogle Scholar
  8. 8.
    Surani MA, Hayashi K, Hajkova P (2007) Genetic and epigenetic regulators of pluripotency. Cell 128(4):747–762PubMedCrossRefGoogle Scholar
  9. 9.
    Li M, Liu GH, Belmonte JC (2012) Navigating the epigenetic landscape of pluripotent stem cells. Nat Rev Mol Cell Biol 13(8):524–535PubMedCrossRefGoogle Scholar
  10. 10.
    Kar S, Deb M, Sengupta D, Shilpi A, Parbin S, Torrisani J, Pradhan S, Patra SK (2012) An insight into the various regulatory mechanisms modulating Human DNA Methyltransferase 1 stability and function. Epigenetics 7(9):994–1007PubMedCrossRefGoogle Scholar
  11. 11.
    Mathews LA, Crea F, Farrar WL (2009) Epigenetic gene regulation in stem cells and correlation to cancer. Differentiation 78(1):1–17PubMedCentralPubMedCrossRefGoogle Scholar
  12. 12.
    Meissner A (2010) Epigenetic modifications in pluripotent and differentiated cells. Nat Biotechnol 28(10):1079–1088PubMedCrossRefGoogle Scholar
  13. 13.
    Wu H, Sun YE (2006) Epigenetic regulation of stem cell differentiation. Pediatr Res 59(4 Pt. 2):21–25CrossRefGoogle Scholar
  14. 14.
    Atkinson S, Armstrong L (2008) Epigenetics in embryonic stem cells: regulation of pluripotency and differentiation. Cell Tissue Res 331(1):23–29PubMedCrossRefGoogle Scholar
  15. 15.
    Lunyak VV, Rosenfeld MG (2008) Epigenetic regulation of stem cell fate. Hum Mol Genet 17(R1):R28–R36PubMedCrossRefGoogle Scholar
  16. 16.
    Cedar H, Bergman Y (2012) Programming of DNA methylation patterns. Annu Rev Biochem 81:97–117PubMedCrossRefGoogle Scholar
  17. 17.
    Huang K, Fan G (2010) DNA methylation in cell differentiation and reprogramming: an emerging systematic view. Regen Med 5(4):531–544PubMedCrossRefGoogle Scholar
  18. 18.
    Meissner A, Mikkelsen TS, Gu H, Wernig M, Hanna J, Sivachenko A, Zhang X, Bernstein BE, Nusbaum C, Jaffe DB, Gnirke A, Jaenisch R, Lander ES (2008) Genome-scale DNA methylation maps of pluripotent and differentiated cells. Nature 454(7205):766–770PubMedCentralPubMedGoogle Scholar
  19. 19.
    Patra SK, Patra A, Rizzi F, Ghosh TC, Bettuzzi S (2008) Demethylation of (cytosine-5-Cmethyl) DNA and regulation of transcription in the epigenetic pathways of cancer development. Cancer Metast Rev 27(2):315–334CrossRefGoogle Scholar
  20. 20.
    Patra SK, Bettuzzi S (2009) Epigenetic DNA-(Cytosine-5-carbon) Modifications: 5-Aza-2′-deoxyctyidine and DNA modification. Biochemistry (Moscow) 74(6):613–619CrossRefGoogle Scholar
  21. 21.
    Seisenberger S, Peat JR, Hore TA, Santos F, Dean W, Reik W (2013) Reprogramming DNA methylation in the mammalian life cycle: building and breaking epigenetic barriers. Philos Trans R Soc Lond B Biol Sci 368(1609):20110330PubMedCrossRefGoogle Scholar
  22. 22.
    Hemberger M, Dean W, Reik W (2009) Epigenetic dynamics of stem cells and cell lineage commitment: digging Waddington’s canal. Nat Rev Mol Cell Biol 10(8):526–537PubMedCrossRefGoogle Scholar
  23. 23.
    Arney KL, Erhardt S, Drewell RA, Surani MA (2001) Epigenetic reprogramming of the genome—from the germ line to the embryo and back again. Int J Dev Biol 45(3):533–540PubMedGoogle Scholar
  24. 24.
    Mayer W, Niveleau A, Walter J, Fundele R, Haaf T (2000) Demethylation of the zygotic paternal genome. Nature 403(6769):501–502PubMedCrossRefGoogle Scholar
  25. 25.
    Oswald J, Engemann S, Lane N, Mayer W, Olek A, Fundele R, Dean W, Reik W, Walter J (2000) Active demethylation of the paternal genome in the mouse zygote. Curr Biol 10(8):475–478PubMedCrossRefGoogle Scholar
  26. 26.
    Hajkova P (2011) Epigenetic reprogramming in the germline: towards the ground state of the epigenome. Philos Trans R Soc Lond B Biol Sci 366(1575):2266–2273PubMedCrossRefGoogle Scholar
  27. 27.
    Santos F, Hendrich B, Reik W, Dean W (2002) Dynamic reprogramming of DNA methylation in the early mouse embryo. Dev Biol 241(1):172–182PubMedCrossRefGoogle Scholar
  28. 28.
    Donnison M, Beaton A, Davey HW, Broadhurst R, L’huillier P, Pfeffer PL (2005) Loss of the extra-embryonic ectoderm in Elf5 mutants leads to defects in embryonic patterning. Development 132(10):2299–2308PubMedCrossRefGoogle Scholar
  29. 29.
    Ng RK, Dean W, Dawson C, Lucifero D, Madeja Z, Reik W, Hemberger M (2008) Epigenetic restriction of embryonic cell lineage fate by methylation of Elf5. Nat Cell Biol 10(11):1280–1290PubMedCentralPubMedCrossRefGoogle Scholar
  30. 30.
    Kwon GS, Viotti M, Hadjantonakis AK (2008) The endoderm of the mouse embryo arises by dynamic widespread intercalation of embryonic and extra-embryonic lineages. Dev Cell 15(4):509–520PubMedCentralPubMedCrossRefGoogle Scholar
  31. 31.
    Ng JH, Heng JC, Loh YH, Ng HH (2008) Transcriptional and epigenetic regulations of embryonic stem cells. Mutat Res 647(1–2):52–58PubMedCrossRefGoogle Scholar
  32. 32.
    Hackett JA, Zylicz JJ, Surani MA (2012) Parallel mechanisms of epigenetic reprogramming in the germline. Trends Genet 28(4):164–174PubMedCrossRefGoogle Scholar
  33. 33.
    Morgan HD, Dean W, Coker HA, Reik W, Petersen-Mahrt SK (2004) Activation-induced cytidine deaminase deaminates 5-methylcytosine in DNA and is expressed in pluripotent tissues: implications for epigenetic reprogramming. J Biol Chem 279(50):52353–52360PubMedCrossRefGoogle Scholar
  34. 34.
    Seki Y, Hayashi K, Itoh K, Mizugaki M, Saitou M, Matsui Y (2005) Extensive and orderly reprogramming of genome-wide chromatin modifications associated with specification and early development of germ cells in mice. Dev Biol 278(2):440–458PubMedCrossRefGoogle Scholar
  35. 35.
    Bao S, Tang F, Li X, Hayashi K, Gillich A, Lao K, Surani MA (2009) Epigenetic reversion of post-implantation epiblast to pluripotent embryonic stem cells. Nature 461(7268):1292–1295PubMedCrossRefGoogle Scholar
  36. 36.
    Maatouk DM, Kellam LD, Mann MR, Lei H, Li E, Bartolomei MS, Resnick JL (2006) DNA methylation is a primary mechanism for silencing post migratory primordial germ cell genes in both germ cell and somatic cell lineages. Development 133(17):3411–3418PubMedCrossRefGoogle Scholar
  37. 37.
    Lees-Murdock DJ, De Felici M, Walsh CP (2003) Methylation dynamics of repetitive DNA elements in the mouse germ cell lineage. Genomics 82(2):230–237PubMedCrossRefGoogle Scholar
  38. 38.
    Hajkova P, Erhardt S, Lane N, Haaf T, El-Maarri O, Reik W, Walter J, Surani MA (2002) Epigenetic reprogramming in mouse primordial germ cells. Mech Dev 117(1–2):15–23PubMedCrossRefGoogle Scholar
  39. 39.
    Szabo PE, Hubner K, Scholer H, Mann JR (2002) Allele-specific expression of imprinted genes in mouse migratory primordial germ cells. Mech Dev 115(1–2):157–160PubMedCrossRefGoogle Scholar
  40. 40.
    Lees-Murdock DJ, Walsh CP (2008) DNA methylation reprogramming in the germ line. Epigenetics 3(1):5–13PubMedCrossRefGoogle Scholar
  41. 41.
    Borgel J, Guibert S, Li Y, Chiba H, Schubeler D, Sasaki H, Forne T, Weber M (2010) Targets and dynamics of promoter DNA methylation during early mouse development. Nat Genet 42(12):1093–1100PubMedCrossRefGoogle Scholar
  42. 42.
    Hackett JA, Reddington JP, Nestor CE, Dunican DS, Branco MR, Reichmann J, Reik W, Surani MA, Adams IR, Meehan RR (2012) Promoter DNA methylation couples genome-defense mechanisms to epigenetic reprogramming in the mouse germline. Development 139(19):3623–3632PubMedCrossRefGoogle Scholar
  43. 43.
    Eilertsen KJ, Floyd Z, Gimble JM (2008) The epigenetics of adult (somatic) stem cells. Crit Rev Eukaryot Gene Expr 18(3):189–206PubMedCentralPubMedCrossRefGoogle Scholar
  44. 44.
    Hochedlinger K, Plath K (2009) Epigenetic reprogramming and induced pluripotency. Development 136(4):509–523PubMedCrossRefGoogle Scholar
  45. 45.
    Rice KL, Hormaeche I, Licht JD (2007) Epigenetic regulation of normal and malignant haematopoiesis. Oncogene 26(47):6697–6714PubMedCrossRefGoogle Scholar
  46. 46.
    Bocker MT, Hellwig I, Breiling A, Eckstein V, Ho AD, Lyko F (2011) Genome-wide promoter DNA methylation dynamics of human hematopoietic progenitor cells during differentiation and aging. Blood 117(19):e182–e189PubMedCrossRefGoogle Scholar
  47. 47.
    Suarez-Alvarez B, Rodriguez RM, Fraga MF, Lopez-Larrea C (2012) DNA methylation: a promising landscape for immune system-related diseases. Trends Genet 28(10):506–514PubMedCrossRefGoogle Scholar
  48. 48.
    Iwasaki H, Mizuno S, Arinobu Y, Ozawa H, Mori Y, Shigematsu H, Takatsu K, Tenen DG, Akashi K (2006) The order of expression of transcription factors direct hierarchical specification of hematopoietic lineages. Genes Dev 20(21):3010–3021PubMedCrossRefGoogle Scholar
  49. 49.
    Calvanese V, Fernandez AF, Urdinguio RG, Suarez-Alvarez B, Mangas C, Perez-Garcia V, Bueno C, Montes R, Ramos-Mejia V, Martinez-Camblor P, Ferrero C, Assenov Y, Bock C, Menendez P, Carrera AC, Lopez-Larrea C, Fraga MF (2012) A promoter DNA demethylation landscape of human hematopoietic differentiation. Nucleic Acids Res 40(1):116–131PubMedCentralPubMedCrossRefGoogle Scholar
  50. 50.
    Lubbert M, Miller CW, Koeffler HP (1991) Changes of DNA methylation and chromatin structure in the human myeloperoxidase gene during myeloid differentiation. Blood 78(2):345–356PubMedGoogle Scholar
  51. 51.
    Zhu J, Emerson SG (2002) Hematopoietic cytokines, transcription factors and lineage commitment. Oncogene 21(21):3295–3313PubMedCrossRefGoogle Scholar
  52. 52.
    Ji H, Ehrlich LI, Seita J, Murakami P, Doi A, Lindau P, Lee H, Aryee MJ, Irizarry RA, Kim K, Rossi DJ, Inlay MA, Serwold T, Karsunky H, Ho L, Daley GQ, Weissman IL, Feinberg AP (2010) Comprehensive methylome map of lineage commitment from haematopoietic progenitors. Nature 467(7313):338–342PubMedCentralPubMedCrossRefGoogle Scholar
  53. 53.
    Cedar H, Bergman Y (2011) Epigenetics of haematopoietic cell development. Nat Rev Immunol 11(7):478–488PubMedCrossRefGoogle Scholar
  54. 54.
    Broske AM, Vockentanz L, Kharazi S, Huska MR, Mancini E, Scheller M, Kuhl C, Enns A, Prinz M, Jaenisch R, Nerlov C, Leutz A, Andrade-Navarro MA, Jacobsen SE, Rosenbauer F (2009) DNA methylation protects hematopoietic stem cell multipotency from myeloerythroid restriction. Nat Genet 41(11):1207–1215PubMedCrossRefGoogle Scholar
  55. 55.
    Orkin SH, Zon LI (2008) Haematopoiesis: an evolving paradigm for stem cell biology. Cell 132(4):631–644PubMedCentralPubMedCrossRefGoogle Scholar
  56. 56.
    Hupkes M, Jonsson MK, Scheenen WJ, van Rotterdam W, Sotoca AM, van Someren EP, van der Heyden MA, van Veen TA, van Ravestein-van Os RI, Bauerschmidt S, Piek E, Ypey DL, van Zoelen EJ, Dechering KJ (2011) Epigenetics: DNA demethylation promotes skeletal myotube maturation. FASEB J 25(11):3861–3872PubMedCrossRefGoogle Scholar
  57. 57.
    Berdasco M, Melguizo C, Prados J, Gomez A, Alaminos M, Pujana MA, Lopez M, Setien F, Ortiz R, Zafra I, Aranega A, Esteller M (2012) DNA methylation plasticity of human adipose-derived stem cells in lineage commitment. Am J Pathol 181(6):2079–2093PubMedCrossRefGoogle Scholar
  58. 58.
    Faralli H, Dilworth FJ (2012) Turning on myogenin in muscle: a paradigm for understanding mechanisms of tissue-specific gene expression. Comp Funct Genomics. doi: 10.1155/2012/836374 PubMedCentralPubMedGoogle Scholar
  59. 59.
    Saccone V, Puri PL (2010) Epigenetic regulation of skeletal myogenesis. Organogenesis 6(1):48–53PubMedCentralPubMedCrossRefGoogle Scholar
  60. 60.
    Goudenege S, Pisani DF, Wdziekonski B, Di Santo JP, Bagnis C, Dani C, Dechesne CA (2009) Enhancement of myogenic and muscle repair capacities of human adipose-derived stem cells with forced expression of MyoD. Mol Ther 17(6):1064–1072PubMedCrossRefGoogle Scholar
  61. 61.
    Lucarelli M, Fuso A, Strom R, Scarpa S (2001) The dynamics of myogenin site-specific demethylation is strongly correlated with its expression and with muscle differentiation. J Biol Chem 276(10):7500–7506PubMedCrossRefGoogle Scholar
  62. 62.
    Hupkes M, van Someren EP, Middelkamp SH, Piek E, van Zoelen EJ, Dechering KJ (2011) DNA methylation restricts spontaneous multi-lineage differentiation of mesenchymal progenitor cells, but is stable during growth factor-induced terminal differentiation. Biochim Biophys Acta 5:839–849CrossRefGoogle Scholar
  63. 63.
    Furumatsu T, Ozaki T (2010) Epigenetic regulation in chondrogenesis. Acta Med Okayama 64(3):155–161PubMedGoogle Scholar
  64. 64.
    Ezura Y, Sekiya I, Koga H, Muneta T, Noda M (2009) Methylation status of CpG islands in the promoter regions of signature genes during chondrogenesis of human synovium-derived mesenchymal stem cells. Arthritis Rheum 60(5):1416–1426PubMedCrossRefGoogle Scholar
  65. 65.
    Zimmermann P, Boeuf S, Dickhut A, Boehmer S, Olek S, Richter W (2008) Correlation of COL10A1 induction during chondrogenesis of mesenchymal stem cells with demethylation of two CpG sites in the COL10A1 promoter. Arthritis Rheum 58(9):2743–2753PubMedCrossRefGoogle Scholar
  66. 66.
    Zhou GS, Zhang XL, Wu JP, Zhang RP, Xiang LX, Dai LC, Shao JZ (2009) 5-Azacytidine facilitates osteogenic gene expression and differentiation of mesenchymal stem cells by alteration in DNA methylation. Cytotechnology 60:1–3CrossRefGoogle Scholar
  67. 67.
    Teven CM, Liu X, Hu N, Tang N, Kim SH, Huang E, Yang K, Li M, Gao JL, Liu H, Natale RB, Luther G, Luo Q, Wang L, Rames R, Bi Y, Luo J, Luu HH, Haydon RC, Reid RR, He TC (2011) Epigenetic regulation of mesenchymal stem cells: a focus on osteogenic and adipogenic differentiation. Stem Cells Int. doi: 10.4061/2011/201371 PubMedCentralPubMedGoogle Scholar
  68. 68.
    Olynik BM, Rastegar M (2012) The genetic and epigenetic journey of embryonic stem cells into mature neural cells. Front Genet 3:81PubMedCentralPubMedCrossRefGoogle Scholar
  69. 69.
    Golebiewska A, Atkinson SP, Lako M, Armstrong L (2009) Epigenetic landscaping during hESC differentiation to neural cells. Stem Cells 27(6):1298–1308PubMedCrossRefGoogle Scholar
  70. 70.
    Massirer KB, Carromeu C, Griesi-Oliveira K, Muotri AR (2011) Maintenance and differentiation of neural stem cells. Wiley Interdiscip Rev Syst Biol Med 3(1):107–114PubMedCrossRefGoogle Scholar
  71. 71.
    Schneider L, d’Adda di Fagagna F (2012) Neural stem cells exposed to BrdU lose their global DNA methylation and undergo astrocytic differentiation. Nucleic Acids Res 40(12):5332–5342PubMedCentralPubMedCrossRefGoogle Scholar
  72. 72.
    Caplan AI, Bruder SP (2001) Mesenchymal stem cells: building blocks for molecular medicine in the 21st century. Trends Mol Med 7(6):259–264PubMedCrossRefGoogle Scholar
  73. 73.
    Boeuf S, Richter W (2010) Chondrogenesis of mesenchymal stem cells: role of tissue source and inducing factors. Stem Cell Res Ther 1(4):31–40PubMedCentralPubMedCrossRefGoogle Scholar
  74. 74.
    Seo S, Na K (2011) Mesenchymal stem cell-based tissue engineering for chondrogenesis. J Biomed Biotechnol. doi: 10.1155/2011/806891 Google Scholar
  75. 75.
    Collas P (2010) Programming differentiation potential in mesenchymal stem cells. Epigenetics 5(6):476–482PubMedCrossRefGoogle Scholar
  76. 76.
    Patra SK (2008) Ras regulation of DNA methylation and cancer. Exp Cell Res 314(6):1193–1201PubMedCrossRefGoogle Scholar
  77. 77.
    Morgan HD, Dean W, Coker HA, Reik W, Petersen-Mahrt SK (2004) Activation induced cytidine deaminase deaminates 5-methylcytosine in DNA and is expressed in pluripotent tissues: implications for epigenetic reprogramming. J Biol Chem 279(50):52353–52360PubMedCrossRefGoogle Scholar
  78. 78.
    Jiricny J, Menigatti M (2008) DNA Cytosine demethylation: are we getting close? Cell 135(7):1167–1169PubMedCrossRefGoogle Scholar
  79. 79.
    Tahiliani M, Koh KP, Shen Y, Pastor WA, Bandukwala H, Brudno Y, Agarwal S, Iyer LM, Liu DR, Aravind L, Rao A (2009) Conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA by MLL partner TET1. Science 324(5929):930–935PubMedCentralPubMedCrossRefGoogle Scholar
  80. 80.
    Ito S, D’Alessio AC, Taranova OV, Hong K, Sowers LC, Zhang Y (2010) Role of Tet proteins in 5mC to 5hmC conversion, ES cell self-renewal, and ICM specification. Nature 466(7310):1129–1133PubMedCentralPubMedCrossRefGoogle Scholar
  81. 81.
    Barretto G, Schafer A, Marhold J, Stach D, Swaminathan SK, Handa V, Doderlein G, Maltry N, Wu W, Lyko F, Niehrs C (2007) Gadd45a promotes epigenetic gene activation by repair-mediated DNA demethylation. Nature 445(7128):671–675CrossRefGoogle Scholar
  82. 82.
    Rai K, Huggins IJ, James SR, Karpf AR, Jones DA, Cairns BR (2008) DNA demethylation in Zebrafish involves the coupling of a deaminase, a glycosylase, and GADD45. Cell 135(7):1201–1212PubMedCentralPubMedCrossRefGoogle Scholar
  83. 83.
    Niehrs C, Schafer A (2012) Active DNA demethylation by Gadd45 and DNA repair. Trends Cell Biol 22(4):220–227PubMedCrossRefGoogle Scholar
  84. 84.
    Kangaspeska S, Stride B, Metivier R, Polycarpou-Schwarz M, Ibberson D, Carmouche RP, Benes V, Gannon F, Reid G (2008) Transient cyclical methylation of promoter DNA. Nature 452(7183):112–115PubMedCrossRefGoogle Scholar
  85. 85.
    Metivier R, Gallais R, Tiffoche C, Le Peron C, Jurkowska RZ, Carmouche RP, Ibberson D, Barath P, Demay F, Reid G, Benes V, Jeltsch A, Gannon F, Salbert G (2008) Cyclical DNA methylation of a transcriptionally active promoter. Nature 452(7183):45–50PubMedCrossRefGoogle Scholar
  86. 86.
    Ooi SKT, Bestor TH (2008) The colorful history of active DNA demethylation. Cell 133(7):1145–1148PubMedCrossRefGoogle Scholar
  87. 87.
    Wu SC, Zhang Y (2010) Active DNA demethylation: many roads lead to Rome. Nat Rev Mol Cell Biol 11(9):607–620PubMedCentralPubMedCrossRefGoogle Scholar
  88. 88.
    Chen CC, Wang KY, Shen CK (2012) The mammalian de novo DNA methyltransferases DNMT3A and DNMT3B are also DNA 5-hydroxymethylcytosine dehydroxymethylases. J Biol Chem 287(40):33116–33121PubMedCrossRefGoogle Scholar
  89. 89.
    Okada Y, Yamagata K, Hong K, Wakayama T, Zhang Y (2010) A role for the elongator complex in zygotic paternal genome demethylation. Nature 463(7280):554–558PubMedCentralPubMedCrossRefGoogle Scholar
  90. 90.
    Szyf M (2003) Targeting DNA methylation in cancer. Ageing Res Rev 2(3):299–328PubMedCrossRefGoogle Scholar
  91. 91.
    Bhattacharya SK, Ramchandani S, Cervoni N, Szyf M (1999) A mammalian protein with specific demethylase activity for mCpG DNA. Nature 397(6720):579–583PubMedCrossRefGoogle Scholar
  92. 92.
    Patra SK, Patra A, Zhao H, Dahiya R (2002) DNA methyltransferase and demethylase in human prostate cancer. Mol Carcinog 33(3):163–171PubMedCrossRefGoogle Scholar

Copyright information

© Springer Basel 2013

Authors and Affiliations

  • Swayamsiddha Kar
    • 1
  • Sabnam Parbin
    • 1
  • Moonmoon Deb
    • 1
  • Arunima Shilpi
    • 1
  • Dipta Sengupta
    • 1
  • Sandip Kumar Rath
    • 1
  • Madhumita Rakshit
    • 1
  • Aditi Patra
    • 2
  • Samir Kumar Patra
    • 1
    Email author
  1. 1.Epigenetics and Cancer Research Laboratory, Biochemistry and Molecular Biology Group, Department of Life ScienceNational Institute of TechnologyRourkelaIndia
  2. 2.Additional Block Animal Health CentreVeterinary OfficeJalpaiguriIndia

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