Skip to main content
NCBI home page
Neuroscience Bulletin logoLink to Neuroscience Bulletin
. 2008 Feb 1;23(4):241–248. doi: 10.1007/s12264-007-0036-8

Epigenetics and neural stem cell commitment

表观调控与神经干细胞分化

Hai-Liang Tang 1,2, Jian-Hong Zhu 1,2,✉
PMCID: PMC5550588  PMID: 17687400

Abstract

Neural stem cell is presently the research hotspot in neuroscience. Recent progress indicates that epigenetic modulation is closely related to the self-renewal and differentiation of neural stem cell. Epigenetics refer to the study of mitotical/meiotical heritage changes in gene function that cannot be explained by changes in the DNA sequence. Major epigenetic mechanisms include DNA methylation, histone modification, chromatin remodeling, genomic imprinting, and non-coding RNA. In this review, we focus on the new insights into the epigenetic mechanism for neural stem cells fate.

Key words: stem cells, epigenesis, neuron restrictive silencer element, genomic imprinting, H19, non-coding RNA

References

  • [1].Wu C.T., Morris J.R. Genes, genetics and epigenetics: a correspondence. Science. 2001;293:1103–1105. doi: 10.1126/science.293.5532.1103. [DOI] [PubMed] [Google Scholar]
  • [2].Hsieh J., Gage F.H. Epigenetic control of neural stem cell fate. Curr Opin Genet Dev. 2004;14:461–469. doi: 10.1016/j.gde.2004.07.006. [DOI] [PubMed] [Google Scholar]
  • [3].Toru K. Epigenetic alchemy for cell fate conversion. Curr Opin Genet Dev. 2006;16:502–507. doi: 10.1016/j.gde.2006.07.001. [DOI] [PubMed] [Google Scholar]
  • [4].Jaenisch R., Bird A. Epigenetic regulation of gene expression: how the genome integrates intrinsic and environmental signals. Nat Genet. 2003;33(Suppl):245–254. doi: 10.1038/ng1089. [DOI] [PubMed] [Google Scholar]
  • [5].Feng J., Chang H., Li E., Fan G. Dynamic expression of de novo DNA methyltransferases Dnmt3a and Dnmt3b in the central nervous system. J Neurosci Res. 2005;79:734–746. doi: 10.1002/jnr.20404. [DOI] [PubMed] [Google Scholar]
  • [6].Zhao X., Ueba T., Christie B.R., Barkho B., McConnell M.J., Nakashima K., et al. Mice lacking methyl-CpG binding protein 1 have deficits in adult neurogenesis and hippocampal function. Proc Natl Acad Sci USA. 2003;100:6777–6782. doi: 10.1073/pnas.1131928100. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [7].Hendrich B., Guy J., Ramsahoye B., Wilson V.A., Bird A. Closely related proteins MBD2 and MBD3 play distinctive but inter-acting roles in mouse development. Genes Dev. 2001;15:710–723. doi: 10.1101/gad.194101. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [8].Millar C.B., Guy J., Sansom O.J., Selfridge J., MacDougall E., Hendrich B., et al. Enhanced CpG mutability and tumorigenesis in MBD4-deficient mice. Science. 2002;297:403–405. doi: 10.1126/science.1073354. [DOI] [PubMed] [Google Scholar]
  • [9].Jung B.P., Jugloff D.G., Zhang G., Logan R., Brown S., Eubanks J.H. The expression of methyl CpG binding factor MeCP2 correlates with cellular differentiation in the developing rat brain and in cultured cells. J Neurobiol. 2003;55:86–96. doi: 10.1002/neu.10201. [DOI] [PubMed] [Google Scholar]
  • [10].Chen W.G., Chang Q., Lin Y., Meissner A., West A.E., Griffith E.C., et al. Derepression of BDNF transcription involves calcium-dependent phosphorylation of MeCP2. Science. 2003;302:885–889. doi: 10.1126/science.1086446. [DOI] [PubMed] [Google Scholar]
  • [11].Martinowich K., Hattori D., Wu H., Fouse S., He F., Hu Y., et al. DNA methylation-related chromatin remodeling in activitydependent BDNF gene regulation. Science. 2003;302:890–893. doi: 10.1126/science.1090842. [DOI] [PubMed] [Google Scholar]
  • [12].Hsieh J., Gage F.H. Chromatin remodeling in neural development and plasticity. Curr Opin Cell Biol. 2005;17:664–671. doi: 10.1016/j.ceb.2005.09.002. [DOI] [PubMed] [Google Scholar]
  • [13].Jenuwein T., Allis C.D. Translating the histone code. Science. 2001;293:1074–1080. doi: 10.1126/science.1063127. [DOI] [PubMed] [Google Scholar]
  • [14].Shiio Y., Eisenman R.N. Histone sumoylation is associated with transcriptional repression. Proc Natl Acad Sci USA. 2003;100:13225–13230. doi: 10.1073/pnas.1735528100. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [15].Lund A.H., van Lohuizen M. Epigenetics and cancer. Genes Dev. 2004;18:2315–2335. doi: 10.1101/gad.1232504. [DOI] [PubMed] [Google Scholar]
  • [16].Egger G., Liang G., Aparicio A., Jones P.A. Epigenetics in human disease and prospects for epigenetic therapy. Nature. 2004;429:457–463. doi: 10.1038/nature02625. [DOI] [PubMed] [Google Scholar]
  • [17].Vega R.B., Matsuda K., Oh J., Barbosa A.C., Yang X., Meadows E., et al. Histone deacetylase 4 controls chondrocyte hypertrophy during skeletogenesis. Cell. 2004;119:555–566. doi: 10.1016/j.cell.2004.10.024. [DOI] [PubMed] [Google Scholar]
  • [18].Thiagalingam S., Cheng K.H., Lee H.J., Mineva N., Thiagalingam A., Ponte J.F. Histone deacetylases: unique players in shaping the epigenetic histone code. Ann NY Acad Sci. 2003;983:84–100. doi: 10.1111/j.1749-6632.2003.tb05964.x. [DOI] [PubMed] [Google Scholar]
  • [19].Mejat A., Ramond F., Bassel-Duby R., Khochbin S., Olson E.N., Schaeffer L. Histone deacetylase 9 couples neuronal activity to muscle chromatin acetylation and gene expression. Nat Neurosci. 2005;8:313–321. doi: 10.1038/nn1408. [DOI] [PubMed] [Google Scholar]
  • [20].Tsankova N.M., Kumar A., Nestler E.J. Histone modifications at gene promoter regions in rat hippocampus after acute and chronic electroconvulsive seizures. J Neurosci. 2004;24:5603–5610. doi: 10.1523/JNEUROSCI.0589-04.2004. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [21].Song M.R., Ghosh A. FGF2-induced chromatin remodeling regulates CNTF-mediated gene expression and astrocyte differentiation. Nat Neurosci. 2004;7:229–235. doi: 10.1038/nn1192. [DOI] [PubMed] [Google Scholar]
  • [22].Somech R., Izraeli S., J Simon A. Histone deacetylase inhibitors-a new tool to treat cancer. Cancer Treat Rev. 2004;30:461–472. doi: 10.1016/j.ctrv.2004.04.006. [DOI] [PubMed] [Google Scholar]
  • [23].Lee J.H., Hart S.R., Skalnik D.G. Histone deacetylase activity is required for embryonic stem cell differentiation. Genesis. 2004;38:32–38. doi: 10.1002/gene.10250. [DOI] [PubMed] [Google Scholar]
  • [24].Shen S., Li J., Casaccia-Bonnefil P. Histone modifications affect timing of oligodendrocyte progenitor differentiation in the developing rat brain. J Cell Biol. 2005;169:577–589. doi: 10.1083/jcb.200412101. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [25].Hsieh J., Nakashima K., Kuwabara T., Mejia E., Gage F.H. Histone deacetylase inhibition-mediated neuronal differentiation of multipotent adult neural progenitor cells. Proc Natl Acad Sci USA. 2004;101:16659–16664. doi: 10.1073/pnas.0407643101. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [26].Arney K.L. H19 and Igf2—enhancing the confusion? Trends Genet. 2003;19:17–23. doi: 10.1016/S0168-9525(02)00004-5. [DOI] [PubMed] [Google Scholar]
  • [27].Gabory A., Ripoche M.A., Yoshimizu T., Dandolo L. The H19 gene: regulation and function of a non-coding RNA. Cytogenet Genome Res. 2006;113:188–193. doi: 10.1159/000090831. [DOI] [PubMed] [Google Scholar]
  • [28].Rugg-Gunn P.J., Ferguson-Smith A.C., Pedersen R.A. Epigenetic status of human embryonic stem cells. Nat Genet. 2005;37:585–587. doi: 10.1038/ng1556. [DOI] [PubMed] [Google Scholar]
  • [29].Rugg-Gunn P.J., Ferguson-Smith A.C., Pedersen R.A. Human embryonic stem cells as a model for studying epigenetic regulation during early development. Cell cycle. 2005;4:1323–1326. doi: 10.4161/cc.4.10.2076. [DOI] [PubMed] [Google Scholar]
  • [30].Szabo P.E., Tang S.H., Silva F.J., Tsark W.M., Mann J.R. Role of CTCF binding sites in the Igf2/H19 imprinting control region. Mol Cell Biol. 2004;24:4791–4800. doi: 10.1128/MCB.24.11.4791-4800.2004. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [31].Lewis A., Murrell A. Genomic imprinting: CTCF protects the boundaries. Curr Biol. 2004;14:R284–R286. doi: 10.1016/j.cub.2004.03.026. [DOI] [PubMed] [Google Scholar]
  • [32].Delaval K., Feil R. Epigenetic regulation of mammalian genomic imprinting. Curr Opin Genet Dev. 2004;14:188–195. doi: 10.1016/j.gde.2004.01.005. [DOI] [PubMed] [Google Scholar]
  • [33].Kono T., Obata Y., Wu Q., Niwa K., Ono Y., Yamamoto Y., et al. Birth of parthenogenetic mice that can develop to adulthood. Nature. 2004;428:860–864. doi: 10.1038/nature02402. [DOI] [PubMed] [Google Scholar]
  • [34].Sparago A., Cerrato F., Vernucci M., Ferrero G.B., Silengo M.C., Riccio A. Microdeletion in the human H19 DMR result in loss of IGF2 imprinting and Beckwith-Wiedemann syndrome. Nat Genet. 2004;36:958–960. doi: 10.1038/ng1410. [DOI] [PubMed] [Google Scholar]
  • [35].Prawitt D., Enklaar T., Gartner-Rupprecht B., Spangenberg C., Oswald M., Lausch E., et al. Microdeletion of target sites for insulator protein CTCF in a chromosome 11p15 imprinting center in Beckwith-Wiedemann syndrome and Wilms’ tumor. Proc Natl Acad Sci USA. 2005;102:4085–4090. doi: 10.1073/pnas.0500037102. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [36].Cho K.S., Elizondo L.I., Boerkoel C.F. Advances in chromatin remodeling and human disease. Curr Opin Genet Dev. 2004;14:308–315. doi: 10.1016/j.gde.2004.04.015. [DOI] [PubMed] [Google Scholar]
  • [37].Langst G., Becker P.B. Nucleosome remodeling: one mechanism, many phenomena? Biochim Biophys Acta. 2004;1677:58–63. doi: 10.1016/j.bbaexp.2003.10.011. [DOI] [PubMed] [Google Scholar]
  • [38].Muller C., Calkhoven C.F., Sha X., Leutz A. The CCAAT enhancer-binding protein α (CEBPα) requires a SWI/SNF complex for proliferation arrest. J Biol Chem. 2004;279:7353–7358. doi: 10.1074/jbc.M312709200. [DOI] [PubMed] [Google Scholar]
  • [39].Kondo T., Raff M. Chromatin remodeling and histone modification in the conversion of oligodendrocyte precursors to neural stem cells. Genes Dev. 2004;18:2963–2972. doi: 10.1101/gad.309404. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [40].Seo S., Richardson G.A., Kroll K.L. The SWI/SNF chromatin remodeling protein Brg1 is required for vertebrate neurogenesis and mediates transactivation of Ngn and NeuroD. Development. 2005;132:105–115. doi: 10.1242/dev.01548. [DOI] [PubMed] [Google Scholar]
  • [41].Molofsky A.V., He S., Bydon M., Morrison S.J., Pardal R. Bmi-1 promotes neural stem cell self-renewal and neural development but not mouse growth and survival by repressing the p16Ink4a and p19Arf senescence pathways. Genes Dev. 2005;19:1432–1437. doi: 10.1101/gad.1299505. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [42].Crosio C., Heitz E., Allis C.D., Borrelli E., Sassone-Corsi P. Chromatin remodeling and neuronal response: multiple signaling pathways induce specific histone H3 modifications and early gene expression in hippocampal neurons. J Cell Sci. 2003;116(Pt24):4905–4914. doi: 10.1242/jcs.00804. [DOI] [PubMed] [Google Scholar]
  • [43].Harfe B.D. MicroRNAs in vertebrate development. Curr Opin Genet Dev. 2005;15:410–415. doi: 10.1016/j.gde.2005.06.012. [DOI] [PubMed] [Google Scholar]
  • [44].Grewal S.I., Moazed D. Heterochromatin and epigenetic control of gene expression. Science. 2003;301:798–802. doi: 10.1126/science.1086887. [DOI] [PubMed] [Google Scholar]
  • [45].Chang S., Johnston R.J., Frøkjaer-Jensen C., Lockery S., Hobert O. MicroRNAs act sequentially and asymmetrically to control chemosensory laterality in the nematode. Nature. 2004;430:785–789. doi: 10.1038/nature02752. [DOI] [PubMed] [Google Scholar]
  • [46].Leaman D., Chen P.Y., Fak J., Yalcin A., Pearce M., Unnerstall U., et al. Antisense-mediated depletion reveals essential and specific functions of microRNAs in Drosophila development. Cell. 2005;121:1097–1108. doi: 10.1016/j.cell.2005.04.016. [DOI] [PubMed] [Google Scholar]
  • [47].Giraldez A.J., Cinalli R.M., Glasner M.E., Enright A.J., Thomson J.M., Baskerville S., et al. MicroRNAs regulate brain morphogenesis in zebrafish. Science. 2005;308:833–838. doi: 10.1126/science.1109020. [DOI] [PubMed] [Google Scholar]
  • [48].Yekta S., Shih I.H., Bartel D.P. MicroRNA-directed cleavage of HOXB8 mRNA. Science. 2004;304:594–596. doi: 10.1126/science.1097434. [DOI] [PubMed] [Google Scholar]
  • [49].Zhao Y., Samal E., Srivastava D. Serum response factor regulates a muscle-specific microRNA that targets Hand2 during cardiogenesis. Nature. 2005;436:214–220. doi: 10.1038/nature03817. [DOI] [PubMed] [Google Scholar]
  • [50].Chen C.Z., Li L., Lodish H.F., Bartel D.P. MicroRNAs modulate hematopoietic lineage differentiation. Science. 2004;303:83–86. doi: 10.1126/science.1091903. [DOI] [PubMed] [Google Scholar]
  • [51].He L., Hannon G.J. MicroRNAs: small RNAs with a big role in gene regulation. Nat Rev Genet. 2004;5:522–531. doi: 10.1038/nrg1379. [DOI] [PubMed] [Google Scholar]
  • [52].Bartel D.P. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004;116:281–297. doi: 10.1016/S0092-8674(04)00045-5. [DOI] [PubMed] [Google Scholar]
  • [53].Kim V.N. MicroRNA biogenesis: coordinated cropping and dicing. Nat Rev Mol Cell Biol. 2005;6:376–85. doi: 10.1038/nrm1644. [DOI] [PubMed] [Google Scholar]
  • [54].Kuwabara T., Hsieh J., Nakashima K., Taira K., Gage F.H. A small modulatory dsRNA specifies the fate of adult neural stem cell. Cell. 2004;116:779–793. doi: 10.1016/S0092-8674(04)00248-X. [DOI] [PubMed] [Google Scholar]
  • [55].Ballas N., Battaglioli E., Atouf F., Andres M.E., Chenoweth J., Anderson M.E., et al. Regulation of neuronal traits by a novel transcriptional complex. Neuron. 2001;31:353–365. doi: 10.1016/S0896-6273(01)00371-3. [DOI] [PubMed] [Google Scholar]
  • [56].Chong J. A., Tapia-Ramirez J., Kim S., Toledo-Aral J.J., Zheng Y., Boutros M.C., et al. REST: A mammalian silencer protein that restricts sodium channel gene expression to neurons. Cell. 1995;80:949–957. doi: 10.1016/0092-8674(95)90298-8. [DOI] [PubMed] [Google Scholar]
  • [57].Schoenherr C.J., Anderson D.J. The neuron-restrictive silencer factor (NRSF): a coordinate repressor of multiple neuronspecific genes. Science. 1995;267:1360–1363. doi: 10.1126/science.7871435. [DOI] [PubMed] [Google Scholar]
  • [58].Bruce A.W., Donaldson I.J., Wood I.C., Yerbury S.A., Sadowski M.I., Chapman M., et al. Genome-wide analysis of repressor element 1 silencing transcription factor/neuron-restrictive silencing factor (REST/NRSF) target genes. Proc Natl Acad Sci USA. 2004;101:10458–10463. doi: 10.1073/pnas.0401827101. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [59].Lunyak V.V., Burgess R., Prefontaine G.G., Nelson C., Sze S.H., Chenoweth J., et al. Corepressor-dependent silencing of chromosomal regions encoding neuronal genes. Science. 2002;298:1747–1752. doi: 10.1126/science.1076469. [DOI] [PubMed] [Google Scholar]
  • [60].Su X., Kameoka S., Lentz S., Majumder S. Activation of REST/ NRSF target genes in neural stem cell is sufficient to cause neuronal differentiation. Mol Cell Biol. 2004;24:8018–8025. doi: 10.1128/MCB.24.18.8018-8025.2004. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [61].Naruse Y., Aoki T., Kojima T., Mori N. Neural restrictive silencer factor recruits mSin3 and histone deacetylase complex to repress neuron specific target genes. Proc Natl Acad Sci USA. 1999;96:13691–13696. doi: 10.1073/pnas.96.24.13691. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [62].Jepsen K., Hermanson O., Onami T.M., Gleiberman A.S., Lunyak V., McEvilly R.J., et al. Combinatorial roles of the nuclear receptor corepressor in transcription and development. Cell. 2000;102:753–763. doi: 10.1016/S0092-8674(00)00064-7. [DOI] [PubMed] [Google Scholar]
  • [63].Wang X.F., Yu P.P., Lu P.H. NRSE, NRSF and their modulatory effects on the expression of neuronal-specific genes. Prog Biochem Biophys. 2005;32:595–599. [Google Scholar]
  • [64].Roloff T.C., Nuber U.A. Chromatin, epigenetics and stem cells. Eur J Cell Biol. 2005;84:123–135. doi: 10.1016/j.ejcb.2004.12.013. [DOI] [PubMed] [Google Scholar]
  • [65].Cheng L.C., Tavazoie M., Doetsch F. Stem cells: from epigenetics to microRNAs. Neuron. 2005;46:363–367. doi: 10.1016/j.neuron.2005.04.027. [DOI] [PubMed] [Google Scholar]
  • [66].Ballas N., Grunseich C., Lu D.D., Speh J.C., Mandel G. REST and its corepressors mediate plasticity of neuronal gene chromatin throughout neurogenesis. Cell. 2005;121:645–657. doi: 10.1016/j.cell.2005.03.013. [DOI] [PubMed] [Google Scholar]
  • [67].Conaco C., Otto S., Han J.J., Mandel G. Reciprocal actions of REST and a microRNA promote neuronal identity. Proc Natl Acad Sci USA. 2006;103:2422–2427. doi: 10.1073/pnas.0511041103. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [68].Taupin P. Neurogenesis in the adult central nervous system. C R Biol. 2006;329:465–475. doi: 10.1016/j.crvi.2006.04.001. [DOI] [PubMed] [Google Scholar]
  • [69].Watanabe Y., Kameoka S., Gopalakrishnan V., Aldape K.D., Pan Z.Z., Lang F.F., et al. Conversion of myoblasts to physiologically active neuronal phenotype. Genes Dev. 2004;18:889–900. doi: 10.1101/gad.1179004. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Neuroscience Bulletin are provided here courtesy of Springer

RESOURCES