Role of DNA and RNA N6-adenine methylation in regulating stem cell fate

Current Stem Cell Research and Therapy

Volumn 13, Issue 1, 2018, Pages 31-38

  Wu, Yunshu ^a   Zhou, Chenchen ^a   Yuan, Quan ^a  

^a SICHUAN UNIVERSITY   (China)

Author keywords

Cell differentiation; Epigenetic modification; Eukaryotes; N6 adenine methylation (m6A); Pluripotency; Stem cell

Indexed keywords

5 METHYLCYTOSINE; ADENINE; DNA; METHYLTRANSFERASE; RNA;

CELL DIFFERENTIATION; CELL METABOLISM; DNA REPLICATION; DNA TRANSPOSITION; EMBRYO DEVELOPMENT; EPIGENETICS; GENETIC TRANSCRIPTION; HUMAN; PLURIPOTENT STEM CELL; PRIORITY JOURNAL; REVIEW; RNA METHYLATION; ANIMAL; CELL LINEAGE; CHEMISTRY; CYTOLOGY; DNA METHYLATION; GENE EXPRESSION REGULATION; GENETIC EPIGENESIS; GENETICS; METABOLISM; STEM CELL;

ADENINE; ANIMALS; CELL LINEAGE; DNA; DNA METHYLATION; EPIGENESIS, GENETIC; GENE EXPRESSION REGULATION; HUMANS; METHYLTRANSFERASES; RNA; STEM CELLS;

EID: 85041512868     PISSN: 1574888X     EISSN: None     Source Type: Journal    
DOI: 10.2174/1574888X12666170621125457     Document Type: Review

References (136)

1. Meissner A. Epigenetic modifications in pluripotent and differentiated cells. Nat Biotechnol 2010; 28: 1079-88.
2. Avgustinova A, Benitah SA. Epigenetic control of adult stem cell function. Nat Rev Mol Cell Biol 2016; 17: 643-658.
3. Roy S, Kundu TK. Gene regulatory networks and epigenetic modifications in cell differentiation. IUBMB Life 2014; 66: 100-9.
4. Zhou Y, Kim J,Yuan X, Braun T. Epigenetic modifications of stem cells: a paradigm for the control of cardiac progenitor cells. Circ Res 2011; 109: 1067-81.
5. Hotchkiss RD. The quantitative separation of purines, pyrimidines, and nucleosides by paper chromatography. J Biol Chem 1948; 175: 315-32.
6. Law JA, Jacobsen SE. Establishing, maintaining and modifying DNA methylation patterns in plants and animals. Nat Rev Genet 2010; 11: 204-20.
7. Suzuki MM, Bird A. DNA methylation landscapes: provocative insights from epigenomics. Nat Rev Genet 2008; 9: 465-76.
8. Smith ZD, Meissner A. DNA methylation: roles in mammalian development. Nat Rev Genet 2013; 14: 204-20.
9. Motorin Y, Lyko F, Helm M. 5-methylcytosine in RNA: detection, enzymatic formation and biological functions. Nucleic Acids Res 2010; 38: 1415-30.
10. Hussain S, Aleksic J, Blanco S, Dietmann S, Frye M. Characterizing 5-methylcytosine in the mammalian epitranscriptome. Genome Biol 2013; 14: 215.
11. Jones PA, Takai D. The role of DNA methylation in mammalian epigenetics. Science 2001; 293: 1068-70.
12. Jackson M, Krassowska A, Gilbert N, et al. Severe global DNA hypomethylation blocks differentiation and induces histone hyperacetylation in embryonic stem cells. Mol Cell Biol 2004; 24: 8862-71.
13. Kaneda M, Okano M, Hata K, et al. Essential role for de novo DNA methyltransferase Dnmt3a in paternal and maternal imprinting. Nature 2004; 429: 900-3.
14. Hata K, Okano M, Lei H, Li E. Dnmt3L cooperates with the Dnmt3 family of de novo DNA methyltransferases to establish maternal imprints in mice. Development 2002; 129: 1983-93.
15. 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: 247-57.
16. Vanyushin BF, Belozersky AN, Kokurina NA, Kadirova DX. 5- methylcytosine and 6-methylamino-purine in bacterial DNA. Nature 1968; 218: 1066-7.
17. Fang G, Munera D, Friedman DI, et al. Genome-wide mapping of methylated adenine residues in pathogenic Escherichia coli using single-molecule real-time sequencing. Nat Biotechnol 2012; 30: 1232-9.
18. Vanyushin BF, Tkacheva SG, Belozersky AN. Rare bases in animal DNA. Nature 1970; 225: 948-9.
19. Hattman S, Kenny C, Berger L, Pratt K. Comparative study of DNA methylation in three unicellular eucaryotes. J Bacteriol 1978; 135: 1156-7.
20. Hattman S. DNA-[adenine] methylation in lower eukaryotes. Biochemistry 2005; 70: 670-9.
21. Gorovsky MA, Hattman S, Pleger GL. [6N] methyl adenine in the nuclear DNA of a eucaryote, Tetrahymena pyriformis. J Cell Biol 1973; 56: 697-701.
22. Ashapkin VV, Kutueva LI, Vanyushin BF. The gene for domains rearranged methyltransferase (DRM2) in Arabidopsis thaliana plants is methylated at both cytosine and adenine residues. Febs Lett 2002; 532: 367-72.
23. Lu M, Campbell JL, Boye E, Kleckner N. SeqA: a negative modulator of replication initiation in E. coli. Cell 1994; 77: 413-26.
24. Laengle-Rouault F, Maenhaut-Michel G, Radman M. GATC sequence and mismatch repair in Escherichia coli. EMBO J 1986; 5: 2009-13.
25. Braaten BA, Nou X, Kaltenbach LS, Low DA. Methylation patterns in pap regulatory DNA control pyelonephritis-associated pili phase variation in E. coli. Cell 1994; 76(3): 577-88.
26. Roberts D, Hoopes BC, McClure WR, Kleckner N. IS10 transposition is regulated by DNA adenine methylation. Cell 1985; 43(1): 117-30.
27. Bertani G, Weigle JJ. Host controlled variation in bacterial viruses. J Bacteriol 1953; 65(2): 113-21.
28. Luria SE, Human ML. A nonhereditary, host-induced variation of bacterial viruses. J Bacteriol 1952; 64(4): 557-69.
29. Rocha EPC. Evolutionary role of restriction/modification systems as revealed by comparative genome analysis. Genome Res 2001; 11(6): 946-58.
30. Kobayashi I. Behavior of restriction-modification systems as selfish mobile elements and their impact on genome evolution. Nucleic Acids Res 2001; 29(18): 3742-56.
31. Greer EL, Blanco MA, Gu L, et al. DNA Methylation on N6-Adenine in C.elegans. Cell 2015; 161(4): 868-78.
32. Zhang G, Huang H, Liu D, et al. N6-Methyladenine DNA Modification in Drosophila. Cell 2015; 161(4): 893-906.
33. Wu TP, Wang T, Seetin MG, et al. DNA methylation on N6- adenine in mammalian embryonic stem cells. Nature 2016; 532(7599): 329-33.
34. Koziol MJ, Bradshaw CR, Allen GE, et al. Identification of methylated deoxyadenosines in vertebrates reveals diversity in DNA modifications. Nat Struct Mol Biol 2016; 23: 24-30.
35. Huang W, Xiong J, Yang Y, et al. Determination of DNA adenine methylation in genomes of mammals and plants by liquid chromatography/ mass spectrometry. RSC Adv 2015; 5: 64046-54.
36. Desrosiers R, Friderici K, Rottman F. Identification of methylated nucleosides in messenger RNA from novikoff hepatoma cell. P Natl Acad Sci USA 1974; 71: 3971-5.
37. Grosjean H. Modification and editing of RNA: Historical overview and important facts to remember. In: Grosjean H, Ed. Fine-Tuning of RNA Functions by Modification and Editing. Berlin Heidelberg: Springer-Verlag 2005; pp. 1-22.
38. Wei C-M, Gershowitz A, Moss B. Methylated nucleotides block 5β terminus of HeLa cell messenger RNA. Cell 1975; 4: 379-86.
39. Bokar JA. The biosynthesis and functional roles of methylated nucleosides in eukaryotic mRNA. Fine-tuning of RNA functions by modification and editing. In: Grosjean H, Ed. Berlin Heidelberg: Springer-Verlag 2005; pp. 141-77.
40. Jia G, Fu Y, He C. Reversible RNA adenosine methylation in biological regulation. Trends Genet 2013; 29: 108-15.
41. Yue Y, Liu J, He C. RNA N6-methyladenosine methylation in post-transcriptional gene expression regulation. Gene Dev 2015; 29: 1343-55.
42. Wu Y, Zhang S, Yuan Q. N6-methyladenosine methyltransferases and demethylases: New regulators of stem cell pluripotency and differentiation. Stem Cells Dev 2016; 25: 1050.
43. Fu Y, Luo G, Chen K, et al. N6-methyldeoxyadenosine marks active transcription start sites in Chlamydomonas. Cell 2015; 161: 879-92.
44. Tahiliani M, Koh KP, Shen Y, et al. Conversion of 5-Methylcytosine to 5-Hydroxymethylcytosine in Mammalian DNA by MLL Partner TET1. Science 2009; 324: 930-5.
45. Ito S, D’Alessio AC, Taranova OV, et al. Role of Tet proteins in 5mC to 5hmC conversion, ES-cell self-renewal and inner cell mass specification. Nature 2010; 466: 1129-33.
46. Koh KP, Yabuuchi A, Rao S, et al. Tet1 and Tet2 regulate 5- hydroxymethylcytosine production and cell lineage specification in mouse embryonic stem cells. Cell Stem Cell 2011; 8: 200-13.
47. Jia G, Fu Y, Zhao X, et al. N6-methyladenosine in nuclear RNA is a major substrate of the obesity-associated FTO. Nat Chem Biol 2011; 7: 885-7.
48. Tronche F, Rollier A, Bach I, Weiss MC, Yaniv M. The rat albumin promoter: cooperation with upstream elements is required when binding of APF/HNF1 to the proximal element is partially impaired by mutation or bacterial methylation. Mol Cell Biol 1989; 9: 4759-66.
49. Lichtsteiner S, Schibler U. A glycosylated liver-specific transcription factor stimulates transcription of the albumin gene. Cell 1989; 57: 1179-87.
50. Sugimoto K, Takeda S, Hirochika H. Transcriptional activation mediated by binding of a plant GATA-type zinc finger protein AGP1 to the AG-motif (AGATCCAA) of the wound-inducible Myb gene NtMyb2. Plant J 2003; 36: 550-64.
51. Pratt K, Hattman S. Deoxyribonucleic acid methylation and chromatin organization in Tetrahymena thermophila. Mol Cell Biol 1981; 1: 600-8.
52. Song Q, Ding Z, Liu J, Li Y, Wang H. Theoretical study on the binding mechanism between N6-methyladenine and natural DNA bases. J Mol Model 2013; 19: 1089-98.
53. Zhou C, Liu Y, Li X, Zou J, Zou S. DNA N6-methyladenine demethylase ALKBH1 enhances osteogenic differentiation of human MSCs. Bone Res 2016; 4: 16033.
54. Luo G-Z, Blanco MA, Greer EL, He C, Shi Y. DNA N6- methyladenine a new epigenetic mark in eukaryotes?. Nat Rev 2015; 16: 705-10.
55. Horowitz S, Horowitz A, Nilsen TW, Munns TW, Rottman FM. Mapping of N6-methyladenosine residues in bovine prolactin mRNA. P Natl Acad Sci USA 1984; 81: 5667-71.
56. Dominissini D, Moshitch-Moshkovitz S, Schwartz S, et al. Topology of the human and mouse m6A RNA methylomes revealed by m6A-seq. Nature 2012; 485: 201-6.
57. Meyer KD, Saletore Y, Zumbo P, et al. Comprehensive analysis of mRNA methylation reveals enrichment in 3' UTRs and near stop codons. Cell 2012; 149: 1635-46.
58. Chen T, Hao YJ, Zhang Y, et al. m(6)A RNA methylation is regulated by microRNAs and promotes reprogramming to pluripotency. Cell Stem Cell 2015; 16: 289-301.
59. Hongay CF, Orr-Weaver TL. Drosophila Inducer of MEiosis 4 (IME4) is required for Notch signaling during oogenesis. P Natl Acad Sci USA 2011; 108: 14855-60.
60. Fu Y, Dominissini D, Rechavi G, He C. Gene expression regulation mediated through reversible m(6)A RNA methylation. Nat Rev Genet 2014; 15: 293-306.
61. Perry RP, Kelley DE, Friderici K, Rottman F. The methylated constituents of L cell messenger RNA: evidence for an unusual cluster at the 5' terminus. Cell 1975; 4: 387-94.
62. Wei C-M, Moss B. Nucleotide sequences at the N6- methyladenosine sites of HeLa cell messenger ribonucleic acid. Biochemistry 1977; 16: 1672-6.
63. Csepany T, Lin A, Baldick CJ, Jr., Beemon K. Sequence specificity of mRNA N6-adenosine methyltransferase. J Biol Chem 1990; 265: 20117-22.
64. Ke S, Alemu EA, Mertens C, et al. A majority of m6A residues are in the last exons, allowing the potential for 3' UTR regulation. Gene Dev 2015; 29: 1-17.
65. Bokar JA, Rath-Shambaugh ME, Ludwiczak R, Narayanann P, Rottmanll F. Characterization and partial purification of mRNA N6-adenosine methyltransferase from HeLa cell nuclei. Internal mRNA methylation requires a multisubunit complex. J Biol Chem 1994; 269: 17697-704.
66. Bokar JA, Shambaugh ME, Polayes D, Matera AG, Rottman FM. Purification and cDNA cloning of the AdoMet-binding subunit of the human m6A methyltransferase. RNA 1997; 3: 1233-47.
67. Liu J, Yue Y, Han D, et al. A METTL3-METTL14 complex mediates mammalian nuclear RNA N6-adenosine methylation. Nat Chem Biol 2014; 10: 93-5.
68. Wang Y, Li Y, Toth JI, et al. N6-methyladenosine modification destabilizes developmental regulators in embryonic stem cells. Nat Cell Biol 2014; 16: 191-8.
69. Ping XL, Sun BF, Wang L, et al. Mammalian WTAP is a regulatory subunit of the RNA N6-methyladenosine methyltransferase. Cell Res 2014; 24: 177-89.
70. Wang X, Feng J, Xue Y, et al. Structural basis of N6-adenosine methylation by the METTL3-METTL14 complex. Nature 2016; 534: 575-9.
71. Patil DP, Chen C-K, Pickering BF, et al. m6A RNA methylation promotes XIST-mediated transcriptional repression. Nature 2016; 537(7620): 369-373.
72. Zheng G, Dahl JA, Niu Y, et al. ALKBH5 is a mammalian RNA demethylase that impacts RNA metabolism and mouse fertility. Mol Cell 2013; 49: 18-29.
73. Zhao X, Yang Y, Sun BF, et al. FTO-dependent demethylation of N6-methyladenosine regulates mRNA splicing and is required for adipogenesis. Cell Res 2014; 24: 1403-19.
74. Zhou J, Wan J, Gao X, et al. Dynamic m(6)A mRNA methylation directs translational control of heat shock response. Nature 2015; 526: 591-4.
75. Gerken T, Girard CA, Tung YC, et al. The obesity-associated FTO gene encodes a 2-oxoglutarate-dependent nucleic acid demethylase. Science 2007; 318: 1469-72.
76. Gao X, Shin YH, Li M, et al. The fat mass and obesity associated gene FTO functions in the brain to regulate postnatal growth in mice. PloS One 2010; 5: e14005.
77. Fu Y, Jia G, Pang X, et al. FTO-mediated formation of N6- hydroxymethyladenosine and N6-formyladenosine in mammalian RNA. Nat Commun 2013; 4: 1798.
78. Wang X, Lu Z, Gomez A, et al. N6-methyladenosine-dependent regulation of messenger RNA stability. Nature 2014; 505: 117-20.
79. 6A-containing RNA through direct recruitment of the CCR4-NOT deadenylase complex. Nat Commun 2016; 7: 1-11.
80. Xiao W, Adhikari S, Dahal U, et al. Nuclear m(6)A reader YTHDC1 regulates mRNA splicing. Mol Cell 2016; 61: 1-13.
81. Wang X, Zhao BS, Roundtree IA, et al. N6-methyladenosine modulates messenger RNA translation efficiency. Cell 2015; 161: 1388-99.
82. Shi H, Wang X, Lu Z, et al. YTHDF3 facilitates translation and decay of N6-methyladenosine-modified RNA. Cell Res 2017; 27: 315-28.
83. Li A, Chen YS, Ping XL, et al. Cytoplasmic m6A reader YTHDF3 promotes mRNA translation. Cell Res 2017; 27: 444-7.
84. Lin S, Choe J, Du P, Triboulet R, Gregory RI. The m(6)A methyltransferase METTL3 promotes translation in human cancer cells. Mol Cell 2016; 62: 335-45.
85. Schumann U, Shafik A, Preiss T. METTL3 gains R/W access to the epitranscriptome. Mol Cell 2016; 62: 323-4.
86. Xiang Y, Laurent B, Hsu CH, et al. RNA m6A methylation regulates the ultraviolet-induced DNA damage response. Nature 2017; 543: 573-6.
87. Schwartz S, Mumbach MR, Jovanovic M, et al. Perturbation of m6A writers reveals two distinct classes of mRNA methylation at internal and 5' sites. Cell Rep 2014; 8: 284-96.
88. Roost C, Lynch SR, Batista PJ, et al. Structure and thermodynamics of N6-methyladenosine in RNA: a spring-loaded base modification. J Am Chem Soc 2015; 137: 2107-15.
89. Liu N, Dai Q, Zheng G, et al. N(6)-methyladenosine-dependent RNA structural switches regulate RNA-protein interactions. Nature 2015; 518: 560-4.
90. Zou S, Toh JD, Wong KH, et al. N(6)-Methyladenosine: a conformational marker that regulates the substrate specificity of human demethylases FTO and ALKBH5. Sci Rep 2016; 6: 25677.
91. Alarcon CR, Lee H, Goodarzi H, Halberg N, Tavazoie SF. N6- methyladenosine marks primary microRNAs for processing. Nature 2015; 519: 482-5.
92. Alarcoʼn CR, Goodarzi H, Lee H, et al. HNRNPA2B1 is a mediator of m6A-dependent nuclear RNA processing events. Cell 2015; 162: 1299-308.
93. Fustin JM, Doi M, Yamaguchi Y, et al. RNA-methylationdependent RNA processing controls the speed of the circadian clock. Cell 2013; 155: 793-806.
94. Batista PJ, Molinie B, Wang J, et al. m(6)A RNA modification controls cell fate transition in mammalian embryonic stem cells. Cell Stem Cell 2014; 15: 707-19.
95. Ben-Haim MS, Moshitch-Moshkovitz S, Rechavi G. FTO: linking m6A demethylation to adipogenesis. Cell Res 2015; 25: 3-4.
96. Geula S, Moshitch-Moshkovitz S, Dominissini D, et al. m6A mRNA methylation facilitates resolution of naïve pluripotency toward differentiation. Science 2015; 347: 1002-6.
97. Zhao BS, He C. Fate by RNA methylation: m6A steers stem cell pluripotency. Genome Biol 2015; 16: 1-3.
98. Li L, Zang L, Zhang F, et al. Fat mass and obesity-associated (FTO) protein regulates adult neurogenesis. Hum Mol Genet 2017.
99. Lence T, Akhtar J, Bayer M, et al. m(6)A modulates neuronal functions and sex determination in Drosophila. Nature 2016; 540: 242.
100. Haussmann IU, Bodi Z, Sanchez-Moran E, et al. m(6)A potentiates Sxl alternative pre-mRNA splicing for robust Drosophila sex determination. Nature 2016; 540: 301.
101. Zhang C, Samanta D, Lu H, et al. Hypoxia induces the breast cancer stem cell phenotype by HIF-dependent and ALKBH5- mediated m6A-demethylation of NANOG mRNA. Proc Natl Acad Sci USA 2016; 113: E2047-56.
102. Li Z, Weng H, Su R, et al. FTO plays an oncogenic role in acute myeloid leukemia as a N 6-methyladenosine RNA demethylase. Cancer Cell 2016.
103. Zhang S, Zhao BS, Zhou A, et al. m(6)A demethylase ALKBH5 maintains tumorigenicity of glioblastoma stem-like cells by sustaining FOXM1 expression and cell proliferation program. Cancer Cell 2017; 31: 591.
104. Cui Q, Shi H, Ye P, et al. m6A RNA methylation regulates the self-renewal and tumorigenesis of glioblastoma stem cells. Cell Rep 2017; 18: 2622-34.
105. Kwok CT, Marshall AD, Rasko JE, Wong JJ. Genetic alterations of m(6)A regulators predict poorer survival in acute myeloid leukemia. J Hematol Oncol 2017; 10: 39.
106. Yang Y, Huang W, Huang JT, et al. Increased N6-methyladenosine in human sperm RNA as a risk factor for asthenozoospermia. Sci Rep 2016; 6: 24345.
107. Ratel D, Boisseau S, Davidson SM, et al. The bacterial nucleoside N6-methyldeoxyadenosine induces the differentiation of mammalian tumor cells. Biochem Bioph Res Co 2001; 285: 800-5.
108. Pan Z, Sikandar S, Witherspoon M, et al. Impaired placental trophoblast lineage differentiation in Alkbh1(-/-) mice. Dev Dynam 2008; 237: 316-27.
109. Nordstrand LM, Svard J, Larsen E, et al. Mice lacking Alkbh1 display sex-ratio distortion and unilateral eye defects. PloS One 2010; 5: e13827.
110. Ougland R, Lando D, Jonson I, et al. ALKBH1 is a histone H2A dioxygenase involved in neural differentiation. Stem Cells 2012; 30: 2672-82.
111. Ougland R, Jonson I, Moen MN, et al. Role of ALKBH1 in the core transcriptional network of embryonic stem cells. Cell Physiol Biochem 2016; 38: 173-84.
112. Fadloun A, Le Gras S, Jost B, et al. Chromatin signatures and retrotransposon profiling in mouse embryos reveal regulation of LINE-1 by RNA. Nat Struct Mol Biol 2013; 20: 332-8.
113. Goodier JL, Ostertag EM, Du K, Jr. HHK. A novel active L1 retrotransposon subfamily in the mouse. Genome Res 2001; 11: 1677-85.
114. Goodier JL, Kazazian HH. Retrotransposons revisited: The restraint and rehabilitation of parasites. Cell 2008; 135: 23-35.
115. Yang X, Matsuda K, Bialek P, et al. ATF4 is a substrate of RSK2 and an essential regulator of osteoblast biology; implication for Coffin-Lowry Syndrome. Cell 2004; 117: 387-98.
116. Maupin KA, Droscha CJ, Williams BO. A comprehensive overview of skeletal phenotypes associated with alterations in Wnt/beta-catenin signaling in humans and mice. Bone Res 2013; 1: 27-71.
117. Liu F, Clark W, Luo G, et al. ALKBH1-mediated tRNA demethylation regulates translation. Cell 2016; 167: 816-28.
118. Agarwala SD, Blitzblau HG, Hochwagen A, Fink GR. RNA methylation by the MIS complex regulates a cell fate decision in yeast. PLoS Genet 2012; 8: e1002732.
119. Clancy MJ, Shambaugh ME, Timpte CS, Bokar JA. Induction of sporulation in saccharomyces cerevisiae leads to the formation of N6-methyladenosine in mRNA: A potential mechanism for the activity of the IME4 gene. Nucleic Acids Res 2002; 30: 4509-18.
120. Zhong S, Li H, Bodi Z, et al. MTA is an Arabidopsis messenger RNA adenosine methylase and interacts with a homolog of a sexspecific splicing factor. Plant Cell 2008; 20: 1278-88.
121. Vespa L, Vachon G, Berger F, et al. The immunophilin-interacting protein AtFIP37 from Arabidopsis is essential for plant development and is involved in trichome endoreduplication. Plant Physiol 2004; 134: 1283-92.
122. Schwartz S, Agarwala Sudeep D, Mumbach Maxwell R, et al. High-Resolution mapping reveals a conserved, widespread, dynamic mRNA methylation program in yeast meiosis. Cell 2013; 155: 1409-21.
123. Bodi Z, Zhong S, Mehra S, et al. Adenosine methylation in Arabidopsis mRNA is associated with the 3' end and reduced levels cause developmental defects. Front Plant Sci 2012; 3: 1-10.
124. Aguilo F, Zhang F, Sancho A, et al. Coordination of mA mRNA methylation and gene transcription by ZFP217 regulates pluripotency and reprogramming. Cell Stem Cell 2015; 17: 689-704.
125. Zhao BS, Xiao W, Beadell AV, et al. m6A-dependent maternal mRNA clearance facilitates zebrafish maternal-to-zygotic transition. Nature 2017; 542: 475.
126. Zhang M, Zhang Y, Ma J, et al. The demethylase activity of FTO (fat mass and obesity associated protein) is required for preadipocyte differentiation. PloS One 2015; 10: e0133788.
127. Ho AJ, Stein JL, Hua X, et al. A commonly carried allele of the obesity-related FTO gene is associated with reduced brain volume in the healthy elderly. P Natl Acad Sci USA 2010; 107: 8404.
128. Ito S, Shen L, Dai Q, et al. Tet proteins can convert 5- methylcytosine to 5-formylcytosine and 5-carboxylcytosine. Science 2011; 333: 1300-3.
129. Ficz G, Branco MR, Seisenberger S, et al. Dynamic regulation of 5-hydroxymethylcytosine in mouse ES cells and during differentiation. Nature 2011; 473(7347): 398-402.
130. Pastor WA, Pape UJ, Huang Y, et al. Genome-wide mapping of 5- hydroxymethylcytosine in embryonic stem cells. Nature 2011; 473(7347): 394-7.
131. Wu H, D’Alessio AC, Ito S, et al. Genome-wide analysis of 5- hydroxymethylcytosine distribution reveals its dual function in transcriptional regulation in mouse embryonic stem cells. Gene Dev 2011; 25: 679-84.
132. Jackson A, Vayssiere B, Garcia T, et al. Gene array analysis of Wnt-regulated genes in C3H10T1/2 cells. Bone 2005; 36: 585-98.
133. Guo Q, Chen Y, Guo L, Jiang T, Lin Z. miR-23a/b regulates the balance between osteoblast and adipocyte differentiation in bone marrow mesenchymal stem cells. Bone Res 2016; 4: 16022.
134. Rahman MS, Akhtar N, Jamil HM, Banik RS, Asaduzzaman SM. TGF-β/BMP signaling and other molecular events: regulation of osteoblastogenesis and bone formation. Bone Res 2015; 3: 15005.
135. Wu M, Chen G, Li Y-P. TGF-β and BMP signaling in osteoblast, skeletal development, and bone formation, homeostasis and disease. Bone Res 2016; 4: 16009.
136. Crane JL, Zhao L, Frye JS, et al. IGF-1 Signaling is essential for differentiation of mesenchymal stem cells for peak bone mass. Bone Res 2013; 1: 186.