Skip to main content

Epigenetics in Development, Differentiation and Reprogramming

  • Chapter
  • First Online:
The Functional Nucleus
  • 1250 Accesses

Abstract

The creation of a complex multicellular organism begins with two haploid cells, the sperm and the egg, merging into one diploid cell. The two genomes are first kept separated as two pronuclei (Cantone and Fisher 2013), but soon thereafter join to form the zygote. This totipotent cell will then go through a series of mitotic cleavage divisions, first creating a small mass of cells called the blastula, and then (by day 3.5 in mouse or day 5.5 in human) form the blastocyst, comprised of the outer trophoblast cells and the pluripotent inner cell mass (ICM). The latter will subsequently differentiate into the three germ layers, creating the new developing organism. During differentiation, each cell expresses a different set of genes, according to its location, function, signaling cascades, etc. Since all cells share the exact same genome, epigenetic processes will dictate the silencing/activation of desired genes, and the maintenance of cellular states.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Abad M, Mosteiro L, Pantoja C, Canamero M, Rayon T, Ors I, Grana O, Megias D, Dominguez O, Martinez D, Manzanares M, Ortega S, Serrano M (2013) Reprogramming in vivo produces teratomas and iPS cells with totipotency features. Nature 502(7471):340–345. doi:10.1038/nature12586

    Article  CAS  PubMed  Google Scholar 

  • Anokye-Danso F, Trivedi CM, Juhr D, Gupta M, Cui Z, Tian Y, Zhang Y, Yang W, Gruber PJ, Epstein JA, Morrisey EE (2011) Highly efficient miRNA-mediated reprogramming of mouse and human somatic cells to pluripotency. Cell Stem Cell 8(4):376–388. doi:10.1016/j.stem.2011.03.001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Apostolou E, Hochedlinger K (2013) Chromatin dynamics during cellular reprogramming. Nature 502(7472):462–471. doi:10.1038/nature12749

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Apostolou E, Ferrari F, Walsh RM, Bar-Nur O, Stadtfeld M, Cheloufi S, Stuart HT, Polo JM, Ohsumi TK, Borowsky ML, Kharchenko PV, Park PJ, Hochedlinger K (2013) Genome-wide chromatin interactions of the Nanog locus in pluripotency, differentiation, and reprogramming. Cell Stem Cell 12(6):699–712. doi:10.1016/j.stem.2013.04.013

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bannister AJ, Kouzarides T (2011) Regulation of chromatin by histone modifications. Cell Res 21(3):381–395. doi:10.1038/cr.2011.22

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Barth TK, Imhof A (2010) Fast signals and slow marks: the dynamics of histone modifications. Trends Biochem Sci 35(11):618–626. doi:10.1016/j.tibs.2010.05.006

    Article  CAS  PubMed  Google Scholar 

  • Bernstein BE, Mikkelsen TS, Xie X, Kamal M, Huebert DJ, Cuff J, Fry B, Meissner A, Wernig M, Plath K, Jaenisch R, Wagschal A, Feil R, Schreiber SL, Lander ES (2006) A bivalent chromatin structure marks key developmental genes in embryonic stem cells. Cell 125(2):315–326. doi:10.1016/j.cell.2006.02.041

    Article  CAS  PubMed  Google Scholar 

  • Bhutani N, Brady JJ, Damian M, Sacco A, Corbel SY, Blau HM (2010) Reprogramming towards pluripotency requires AID-dependent DNA demethylation. Nature 463(7284):1042–1047. doi:10.1038/nature08752, nature08752 [pii]

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Biran A, Meshorer E (2012) Concise review: chromatin and genome organization in reprogramming. Stem Cells 30(9):1793–1799. doi:10.1002/stem.1169

    Article  CAS  PubMed  Google Scholar 

  • Blaschke K, Ebata KT, Karimi MM, Zepeda-Martinez JA, Goyal P, Mahapatra S, Tam A, Laird DJ, Hirst M, Rao A, Lorincz MC, Ramalho-Santos M (2013) Vitamin C induces Tet-dependent DNA demethylation and a blastocyst-like state in ES cells. Nature 500(7461):222–226. doi:10.1038/nature12362

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Blau HM, Chiu CP, Webster C (1983) Cytoplasmic activation of human nuclear genes in stable heterocaryons. Cell 32(4):1171–1180

    Article  CAS  PubMed  Google Scholar 

  • Bock C, Kiskinis E, Verstappen G, Gu H, Boulting G, Smith ZD, Ziller M, Croft GF, Amoroso MW, Oakley DH, Gnirke A, Eggan K, Meissner A (2011) Reference Maps of human ES and iPS cell variation enable high-throughput characterization of pluripotent cell lines. Cell 144(3):439–452. doi:10.1016/j.cell.2010.12.032

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Boland MJ, Nazor KL, Loring JF (2014) Epigenetic regulation of pluripotency and differentiation. Circ Res 115(2):311–324. doi:10.1161/CIRCRESAHA.115.301517

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bourc’his D, Xu GL, Lin CS, Bollman B, Bestor TH (2001) Dnmt3L and the establishment of maternal genomic imprints. Science 294(5551):2536–2539. doi:10.1126/science.1065848

    Article  PubMed  Google Scholar 

  • Brogaard K, Xi L, Wang JP, Widom J (2012) A map of nucleosome positions in yeast at base-pair resolution. Nature 486(7404):496–501. doi:10.1038/nature11142

    CAS  PubMed  PubMed Central  Google Scholar 

  • Brons IG, Smithers LE, Trotter MW, Rugg-Gunn P, Sun B, Chuva de Sousa Lopes SM, Howlett SK, Clarkson A, Ahrlund-Richter L, Pedersen RA, Vallier L (2007) Derivation of pluripotent epiblast stem cells from mammalian embryos. Nature 448(7150):191–195. doi:10.1038/nature05950

    Article  CAS  PubMed  Google Scholar 

  • Buganim Y, Faddah DA, Cheng AW, Itskovich E, Markoulaki S, Ganz K, Klemm SL, van Oudenaarden A, Jaenisch R (2012) Single-cell expression analyses during cellular reprogramming reveal an early stochastic and a late hierarchic phase. Cell 150(6):1209–1222. doi:10.1016/j.cell.2012.08.023

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Buganim Y, Faddah DA, Jaenisch R (2013) Mechanisms and models of somatic cell reprogramming. Nat Rev Genet 14(6):427–439. doi:10.1038/nrg3473

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cantone I, Fisher AG (2013) Epigenetic programming and reprogramming during development. Nat Struct Mol Biol 20(3):282–289. doi:10.1038/nsmb.2489

    Article  CAS  PubMed  Google Scholar 

  • Carey BW, Markoulaki S, Hanna J, Saha K, Gao Q, Mitalipova M, Jaenisch R (2009) Reprogramming of murine and human somatic cells using a single polycistronic vector. Proc Natl Acad Sci USA 106(1):157–162. doi:10.1073/pnas.0811426106

    Article  CAS  PubMed  Google Scholar 

  • Carone BR, Hung JH, Hainer SJ, Chou MT, Carone DM, Weng Z, Fazzio TG, Rando OJ (2014) High-resolution mapping of chromatin packaging in mouse embryonic stem cells and sperm. Dev Cell 30(1):11–22. doi:10.1016/j.devcel.2014.05.024

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chan YS, Goke J, Ng JH, Lu X, Gonzales KA, Tan CP, Tng WQ, Hong ZZ, Lim YS, Ng HH (2013) Induction of a human pluripotent state with distinct regulatory circuitry that resembles preimplantation epiblast. Cell Stem Cell 13(6):663–675. doi:10.1016/j.stem.2013.11.015

    Article  CAS  PubMed  Google Scholar 

  • Chen J, Liu H, Liu J, Qi J, Wei B, Yang J, Liang H, Chen Y, Chen J, Wu Y, Guo L, Zhu J, Zhao X, Peng T, Zhang Y, Chen S, Li X, Li D, Wang T, Pei D (2013) H3K9 methylation is a barrier during somatic cell reprogramming into iPSCs. Nat Genet 45(1):34–42. doi:10.1038/ng.2491

    Article  CAS  PubMed  Google Scholar 

  • Christophorou MA, Castelo-Branco G, Halley-Stott RP, Oliveira CS, Loos R, Radzisheuskaya A, Mowen KA, Bertone P, Silva JC, Zernicka-Goetz M, Nielsen ML, Gurdon JB, Kouzarides T (2014) Citrullination regulates pluripotency and histone H1 binding to chromatin. Nature 507(7490):104–108. doi:10.1038/nature12942

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cowley SM, Iritani BM, Mendrysa SM, Xu T, Cheng PF, Yada J, Liggitt HD, Eisenman RN (2005) The mSin3A chromatin-modifying complex is essential for embryogenesis and T-cell development. Mol Cell Biol 25(16):6990–7004. doi:10.1128/MCB.25.16.6990-7004.2005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dawlaty MM, Breiling A, Le T, Barrasa MI, Raddatz G, Gao Q, Powell BE, Cheng AW, Faull KF, Lyko F, Jaenisch R (2014) Loss of Tet enzymes compromises proper differentiation of embryonic stem cells. Dev Cell 29(1):102–111. doi:10.1016/j.devcel.2014.03.003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • de Wit E, Bouwman BA, Zhu Y, Klous P, Splinter E, Verstegen MJ, Krijger PH, Festuccia N, Nora EP, Welling M, Heard E, Geijsen N, Poot RA, Chambers I, de Laat W (2013) The pluripotent genome in three dimensions is shaped around pluripotency factors. Nature 501(7466):227–231. doi:10.1038/nature12420

    Article  PubMed  CAS  Google Scholar 

  • DeVeale B, van der Kooy D, Babak T (2012) Critical evaluation of imprinted gene expression by RNA-Seq: a new perspective. PLoS Genet 8(3):e1002600. doi:10.1371/journal.pgen.1002600

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dixon JR, Selvaraj S, Yue F, Kim A, Li Y, Shen Y, Hu M, Liu JS, Ren B (2012) Topological domains in mammalian genomes identified by analysis of chromatin interactions. Nature 485(7398):376–380. doi:10.1038/nature11082

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • dos Santos RL, Tosti L, Radzisheuskaya A, Caballero IM, Kaji K, Hendrich B, Silva JC (2014) MBD3/NuRD facilitates induction of pluripotency in a context-dependent manner. Cell Stem Cell 15(1):102–110. doi:10.1016/j.stem.2014.04.019

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Dovey OM, Foster CT, Cowley SM (2010) Histone deacetylase 1 (HDAC1), but not HDAC2, controls embryonic stem cell differentiation. Proc Natl Acad Sci USA 107(18):8242–8247. doi:10.1073/pnas.1000478107

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Efroni S, Duttagupta R, Cheng J, Dehghani H, Hoeppner DJ, Dash C, Bazett-Jones DP, Le Grice S, McKay RD, Buetow KH, Gingeras TR, Misteli T, Meshorer E (2008) Global transcription in pluripotent embryonic stem cells. Cell Stem Cell 2(5):437–447. doi:10.1016/j.stem.2008.03.021, S1934-5909(08)00161-6 [pii]

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Evans MJ, Kaufman MH (1981) Establishment in culture of pluripotential cells from mouse embryos. Nature 292(5819):154–156

    Article  CAS  PubMed  Google Scholar 

  • Fan Y, Nikitina T, Zhao J, Fleury TJ, Bhattacharyya R, Bouhassira EE, Stein A, Woodcock CL, Skoultchi AI (2005) Histone H1 depletion in mammals alters global chromatin structure but causes specific changes in gene regulation. Cell 123(7):1199–1212

    Article  CAS  PubMed  Google Scholar 

  • Fazzio TG, Huff JT, Panning B (2008) An RNAi screen of chromatin proteins identifies Tip60-p400 as a regulator of embryonic stem cell identity. Cell 134(1):162–174. doi:10.1016/j.cell.2008.05.031, S0092-8674(08)00692-2 [pii]

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gafni O, Weinberger L, Mansour AA, Manor YS, Chomsky E, Ben-Yosef D, Kalma Y, Viukov S, Maza I, Zviran A, Rais Y, Shipony Z, Mukamel Z, Krupalnik V, Zerbib M, Geula S, Caspi I, Schneir D, Shwartz T, Gilad S, Amann-Zalcenstein D, Benjamin S, Amit I, Tanay A, Massarwa R, Novershtern N, Hanna JH (2013) Derivation of novel human ground state naive pluripotent stem cells. Nature 504(7479):282–286. doi:10.1038/nature12745

    Article  CAS  PubMed  Google Scholar 

  • Gaspar-Maia A, Alajem A, Polesso F, Sridharan R, Mason MJ, Heidersbach A, Ramalho-Santos J, McManus MT, Plath K, Meshorer E, Ramalho-Santos M (2009) Chd1 regulates open chromatin and pluripotency of embryonic stem cells. Nature 460(7257):863–868. doi:10.1038/nature08212, nature08212 [pii]

    CAS  PubMed  PubMed Central  Google Scholar 

  • Gaspar-Maia A, Alajem A, Meshorer E, Ramalho-Santos M (2011) Open chromatin in pluripotency and reprogramming. Nat Rev Mol Cell Biol 12(1):36–47. doi:10.1038/nrm3036, nrm3036 [pii]

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gifford CA, Ziller MJ, Gu H, Trapnell C, Donaghey J, Tsankov A, Shalek AK, Kelley DR, Shishkin AA, Issner R, Zhang X, Coyne M, Fostel JL, Holmes L, Meldrim J, Guttman M, Epstein C, Park H, Kohlbacher O, Rinn J, Gnirke A, Lander ES, Bernstein BE, Meissner A (2013) Transcriptional and epigenetic dynamics during specification of human embryonic stem cells. Cell 153(5):1149–1163. doi:10.1016/j.cell.2013.04.037

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gu TP, Guo F, Yang H, Wu HP, Xu GF, Liu W, Xie ZG, Shi L, He X, Jin SG, Iqbal K, Shi YG, Deng Z, Szabo PE, Pfeifer GP, Li J, Xu GL (2011) The role of Tet3 DNA dioxygenase in epigenetic reprogramming by oocytes. Nature 477(7366):606–610. doi:10.1038/nature10443

    Article  CAS  PubMed  Google Scholar 

  • Guan JS, Haggarty SJ, Giacometti E, Dannenberg JH, Joseph N, Gao J, Nieland TJ, Zhou Y, Wang X, Mazitschek R, Bradner JE, DePinho RA, Jaenisch R, Tsai LH (2009) HDAC2 negatively regulates memory formation and synaptic plasticity. Nature 459(7243):55–60. doi:10.1038/nature07925

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Guo H, Zhu P, Yan L, Li R, Hu B, Lian Y, Yan J, Ren X, Lin S, Li J, Jin X, Shi X, Liu P, Wang X, Wang W, Wei Y, Li X, Guo F, Wu X, Fan X, Yong J, Wen L, Xie SX, Tang F, Qiao J (2014) The DNA methylation landscape of human early embryos. Nature 511(7511):606–610. doi:10.1038/nature13544

    Article  CAS  PubMed  Google Scholar 

  • Gurdon JB, Elsdale TR, Fischberg M (1958) Sexually mature individuals of Xenopus laevis from the transplantation of single somatic nuclei. Nature 182(4627):64–65

    Article  CAS  PubMed  Google Scholar 

  • Haberland M, Montgomery RL, Olson EN (2009) The many roles of histone deacetylases in development and physiology: implications for disease and therapy. Nat Rev Genet 10(1):32–42. doi:10.1038/nrg2485

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hackett JA, Sengupta R, Zylicz JJ, Murakami K, Lee C, Down TA, Surani MA (2013) Germline DNA demethylation dynamics and imprint erasure through 5-hydroxymethylcytosine. Science 339(6118):448–452. doi:10.1126/science.1229277

    Article  CAS  PubMed  Google Scholar 

  • Hanna J, Saha K, Pando B, van Zon J, Lengner CJ, Creyghton MP, van Oudenaarden A, Jaenisch R (2009) Direct cell reprogramming is a stochastic process amenable to acceleration. Nature 462(7273):595–601. doi:10.1038/nature08592

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hezroni H, Sailaja BS, Meshorer E (2011a) Pluripotency-related, valproic acid (VPA)-induced genome-wide histone H3 lysine 9 (H3K9) acetylation patterns in embryonic stem cells. J Biol Chem 286(41):35977–35988. doi:10.1074/jbc.M111.266254

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hezroni H, Tzchori I, Davidi A, Mattout A, Biran A, Nissim-Rafinia M, Westphal H, Meshorer E (2011b) H3K9 histone acetylation predicts pluripotency and reprogramming capacity of ES cells. Nucleus 2(4):300–311

    Article  PubMed  PubMed Central  Google Scholar 

  • Hnisz D, Abraham BJ, Lee TI, Lau A, Saint-Andre V, Sigova AA, Hoke HA, Young RA (2013) Super-enhancers in the control of cell identity and disease. Cell 155(4):934–947. doi:10.1016/j.cell.2013.09.053

    Article  CAS  PubMed  Google Scholar 

  • Ho L, Crabtree GR (2010) Chromatin remodelling during development. Nature 463(7280):474–484. doi:10.1038/nature08911

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ho L, Ronan JL, Wu J, Staahl BT, Chen L, Kuo A, Lessard J, Nesvizhskii AI, Ranish J, Crabtree GR (2009) An embryonic stem cell chromatin remodeling complex, esBAF, is essential for embryonic stem cell self-renewal and pluripotency. Proc Natl Acad Sci USA 106(13):5181–5186. doi:10.1073/pnas.0812889106

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ho L, Miller EL, Ronan JL, Ho WQ, Jothi R, Crabtree GR (2011) esBAF facilitates pluripotency by conditioning the genome for LIF/STAT3 signalling and by regulating polycomb function. Nat Cell Biol 13(8):903–913. doi:10.1038/ncb2285

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hou C, Li L, Qin ZS, Corces VG (2012) Gene density, transcription, and insulators contribute to the partition of the Drosophila genome into physical domains. Mol Cell 48(3):471–484. doi:10.1016/j.molcel.2012.08.031

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hou P, Li Y, Zhang X, Liu C, Guan J, Li H, Zhao T, Ye J, Yang W, Liu K, Ge J, Xu J, Zhang Q, Zhao Y, Deng H (2013) Pluripotent stem cells induced from mouse somatic cells by small-molecule compounds. Science 341(6146):651–654. doi:10.1126/science.1239278

    Article  CAS  PubMed  Google Scholar 

  • Howell CY, Bestor TH, Ding F, Latham KE, Mertineit C, Trasler JM, Chaillet JR (2001) Genomic imprinting disrupted by a maternal effect mutation in the Dnmt1 gene. Cell 104(6):829–838

    Article  CAS  PubMed  Google Scholar 

  • Hu X, Zhang L, Mao SQ, Li Z, Chen J, Zhang RR, Wu HP, Gao J, Guo F, Liu W, Xu GF, Dai HQ, Shi YG, Li X, Hu B, Tang F, Pei D, Xu GL (2014) Tet and TDG mediate DNA demethylation essential for mesenchymal-to-epithelial transition in somatic cell reprogramming. Cell Stem Cell 14(4):512–522. doi:10.1016/j.stem.2014.01.001

    Article  CAS  PubMed  Google Scholar 

  • Huangfu D, Maehr R, Guo W, Eijkelenboom A, Snitow M, Chen AE, Melton DA (2008a) Induction of pluripotent stem cells by defined factors is greatly improved by small-molecule compounds. Nat Biotechnol 26(7):795–797. doi:10.1038/nbt1418, nbt1418 [pii]

    Article  CAS  PubMed  Google Scholar 

  • Huangfu D, Osafune K, Maehr R, Guo W, Eijkelenboom A, Chen S, Muhlestein W, Melton DA (2008b) Induction of pluripotent stem cells from primary human fibroblasts with only Oct4 and Sox2. Nat Biotechnol 26(11):1269–1275. doi:10.1038/nbt.1502

    Article  CAS  PubMed  Google Scholar 

  • Humphrey GW, Wang Y, Russanova VR, Hirai T, Qin J, Nakatani Y, Howard BH (2001) Stable histone deacetylase complexes distinguished by the presence of SANT domain proteins CoREST/kiaa0071 and Mta-L1. J Biol Chem 276(9):6817–6824. doi:10.1074/jbc.M007372200

    Article  CAS  PubMed  Google Scholar 

  • Hussein SM, Batada NN, Vuoristo S, Ching RW, Autio R, Narva E, Ng S, Sourour M, Hamalainen R, Olsson C, Lundin K, Mikkola M, Trokovic R, Peitz M, Brustle O, Bazett-Jones DP, Alitalo K, Lahesmaa R, Nagy A, Otonkoski T (2011) Copy number variation and selection during reprogramming to pluripotency. Nature 471(7336):58–62. doi:10.1038/nature09871

    Article  CAS  PubMed  Google Scholar 

  • Ichida JK, Blanchard J, Lam K, Son EY, Chung JE, Egli D, Loh KM, Carter AC, Di Giorgio FP, Koszka K, Huangfu D, Akutsu H, Liu DR, Rubin LL, Eggan K (2009) A small-molecule inhibitor of tgf-Beta signaling replaces sox2 in reprogramming by inducing nanog. Cell Stem Cell 5(5):491–503. doi:10.1016/j.stem.2009.09.012

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jackson M, Krassowska A, Gilbert N, Chevassut T, Forrester L, Ansell J, Ramsahoye B (2004) Severe global DNA hypomethylation blocks differentiation and induces histone hyperacetylation in embryonic stem cells. Mol Cell Biol 24(20):8862–8871

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jamaladdin S, Kelly RD, O’Regan L, Dovey OM, Hodson GE, Millard CJ, Portolano N, Fry AM, Schwabe JW, Cowley SM (2014) Histone deacetylase (HDAC) 1 and 2 are essential for accurate cell division and the pluripotency of embryonic stem cells. Proc Natl Acad Sci USA 111(27):9840–9845. doi:10.1073/pnas.1321330111

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kaji K, Caballero IM, MacLeod R, Nichols J, Wilson VA, Hendrich B (2006) The NuRD component Mbd3 is required for pluripotency of embryonic stem cells. Nat Cell Biol 8(3):285–292

    Article  CAS  PubMed  Google Scholar 

  • Kaji K, Nichols J, Hendrich B (2007) Mbd3, a component of the NuRD co-repressor complex, is required for development of pluripotent cells. Development 134(6):1123–1132. doi:10.1242/dev.02802

    Article  CAS  PubMed  Google Scholar 

  • Kidder BL, Palmer S (2012) HDAC1 regulates pluripotency and lineage specific transcriptional networks in embryonic and trophoblast stem cells. Nucleic Acids Res 40(7):2925–2939. doi:10.1093/nar/gkr1151

    Article  CAS  PubMed  Google Scholar 

  • Kobayashi H, Sakurai T, Imai M, Takahashi N, Fukuda A, Yayoi O, Sato S, Nakabayashi K, Hata K, Sotomaru Y, Suzuki Y, Kono T (2012) Contribution of intragenic DNA methylation in mouse gametic DNA methylomes to establish oocyte-specific heritable marks. PLoS Genet 8(1):e1002440. doi:10.1371/journal.pgen.1002440

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Koche RP, Smith ZD, Adli M, Gu H, Ku M, Gnirke A, Bernstein BE, Meissner A (2011) Reprogramming factor expression initiates widespread targeted chromatin remodeling. Cell Stem Cell 8(1):96–105. doi:10.1016/j.stem.2010.12.001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kramer OH, Zhu P, Ostendorff HP, Golebiewski M, Tiefenbach J, Peters MA, Brill B, Groner B, Bach I, Heinzel T, Gottlicher M (2003) The histone deacetylase inhibitor valproic acid selectively induces proteasomal degradation of HDAC2. EMBO J 22(13):3411–3420. doi:10.1093/emboj/cdg315

    Article  PubMed  PubMed Central  Google Scholar 

  • Kurdistani SK, Robyr D, Tavazoie S, Grunstein M (2002) Genome-wide binding map of the histone deacetylase Rpd3 in yeast. Nat Genet 31(3):248–254. doi:10.1038/ng907

    Article  CAS  PubMed  Google Scholar 

  • Laherty CD, Yang WM, Sun JM, Davie JR, Seto E, Eisenman RN (1997) Histone deacetylases associated with the mSin3 corepressor mediate mad transcriptional repression. Cell 89(3):349–356

    Article  CAS  PubMed  Google Scholar 

  • Landry J, Sharov AA, Piao Y, Sharova LV, Xiao H, Southon E, Matta J, Tessarollo L, Zhang YE, Ko MS, Kuehn MR, Yamaguchi TP, Wu C (2008) Essential role of chromatin remodeling protein Bptf in early mouse embryos and embryonic stem cells. PLoS Genet 4(10):e1000241. doi:10.1371/journal.pgen.1000241

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Laurent L, Wong E, Li G, Huynh T, Tsirigos A, Ong CT, Low HM, Kin Sung KW, Rigoutsos I, Loring J, Wei CL (2010) Dynamic changes in the human methylome during differentiation. Genome Res 20(3):320–331. doi:10.1101/gr.101907.109

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lee JT, Bartolomei MS (2013) X-inactivation, imprinting, and long noncoding RNAs in health and disease. Cell 152(6):1308–1323. doi:10.1016/j.cell.2013.02.016

    Article  CAS  PubMed  Google Scholar 

  • Lee CK, Shibata Y, Rao B, Strahl BD, Lieb JD (2004) Evidence for nucleosome depletion at active regulatory regions genome-wide. Nat Genet 36(8):900–905. doi:10.1038/ng1400

    Article  CAS  PubMed  Google Scholar 

  • Li E, Bestor TH, Jaenisch R (1992) Targeted mutation of the DNA methyltransferase gene results in embryonic lethality. Cell 69(6):915–926

    Article  CAS  PubMed  Google Scholar 

  • Li R, Liang J, Ni S, Zhou T, Qing X, Li H, He W, Chen J, Li F, Zhuang Q, Qin B, Xu J, Li W, Yang J, Gan Y, Qin D, Feng S, Song H, Yang D, Zhang B, Zeng L, Lai L, Esteban MA, Pei D (2010) A mesenchymal-to-epithelial transition initiates and is required for the nuclear reprogramming of mouse fibroblasts. Cell Stem Cell 7(1):51–63. doi:10.1016/j.stem.2010.04.014

    Article  CAS  PubMed  Google Scholar 

  • Li X, Li L, Pandey R, Byun JS, Gardner K, Qin Z, Dou Y (2012) The histone acetyltransferase MOF is a key regulator of the embryonic stem cell core transcriptional network. Cell Stem Cell 11(2):163–178. doi:10.1016/j.stem.2012.04.023

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Liang G, Taranova O, Xia K, Zhang Y (2010) Butyrate promotes induced pluripotent stem cell generation. J Biol Chem 285(33):25516–25521. doi:10.1074/jbc.M110.142059

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liang G, He J, Zhang Y (2012) Kdm2b promotes induced pluripotent stem cell generation by facilitating gene activation early in reprogramming. Nat Cell Biol 14(5):457–466. doi:10.1038/ncb2483

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lin CY, Loven J, Rahl PB, Paranal RM, Burge CB, Bradner JE, Lee TI, Young RA (2012) Transcriptional amplification in tumor cells with elevated c-Myc. Cell 151(1):56–67. doi:10.1016/j.cell.2012.08.026

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lister R, Pelizzola M, Dowen RH, Hawkins RD, Hon G, Tonti-Filippini J, Nery JR, Lee L, Ye Z, Ngo QM, Edsall L, Antosiewicz-Bourget J, Stewart R, Ruotti V, Millar AH, Thomson JA, Ren B, Ecker JR (2009) Human DNA methylomes at base resolution show widespread epigenomic differences. Nature 462(7271):315–322. doi:10.1038/nature08514, nature08514 [pii]

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lister R, Pelizzola M, Kida YS, Hawkins RD, Nery JR, Hon G, Antosiewicz-Bourget J, O’Malley R, Castanon R, Klugman S, Downes M, Yu R, Stewart R, Ren B, Thomson JA, Evans RM, Ecker JR (2011) Hotspots of aberrant epigenomic reprogramming in human induced pluripotent stem cells. Nature 471(7336):68–73. doi:10.1038/nature09798

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lister R, Mukamel EA, Nery JR, Urich M, Puddifoot CA, Johnson ND, Lucero J, Huang Y, Dwork AJ, Schultz MD, Yu M, Tonti-Filippini J, Heyn H, Hu S, Wu JC, Rao A, Esteller M, He C, Haghighi FG, Sejnowski TJ, Behrens MM, Ecker JR (2013) Global epigenomic reconfiguration during mammalian brain development. Science 341(6146):1237905. doi:10.1126/science.1237905

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Livyatan I, Meshorer E (2013) The HDAC interaction network. Mol Syst Biol 9:671. doi:10.1038/msb.2013.33

    Article  PubMed  PubMed Central  Google Scholar 

  • Lorthongpanich C, Cheow LF, Balu S, Quake SR, Knowles BB, Burkholder WF, Solter D, Messerschmidt DM (2013) Single-cell DNA-methylation analysis reveals epigenetic chimerism in preimplantation embryos. Science 341(6150):1110–1112. doi:10.1126/science.1240617

    Article  CAS  PubMed  Google Scholar 

  • Luo M, Ling T, Xie W, Sun H, Zhou Y, Zhu Q, Shen M, Zong L, Lyu G, Zhao Y, Ye T, Gu J, Tao W, Lu Z, Grummt I (2013) NuRD blocks reprogramming of mouse somatic cells into pluripotent stem cells. Stem Cells 31(7):1278–1286. doi:10.1002/stem.1374

    Article  CAS  PubMed  Google Scholar 

  • Mali P, Chou BK, Yen J, Ye Z, Zou J, Dowey S, Brodsky RA, Ohm JE, Yu W, Baylin SB, Yusa K, Bradley A, Meyers DJ, Mukherjee C, Cole PA, Cheng L (2010) Butyrate greatly enhances derivation of human induced pluripotent stem cells by promoting epigenetic remodeling and the expression of pluripotency-associated genes. Stem Cells 28(4):713–720. doi:10.1002/stem.402

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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):766–770. doi:10.1038/nature07107

    CAS  PubMed  PubMed Central  Google Scholar 

  • Mekhoubad S, Bock C, de Boer AS, Kiskinis E, Meissner A, Eggan K (2012) Erosion of dosage compensation impacts human iPSC disease modeling. Cell Stem Cell 10(5):595–609. doi:10.1016/j.stem.2012.02.014

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Melcer S, Hezroni H, Rand E, Nissim-Rafinia M, Skoultchi A, Stewart CL, Bustin M, Meshorer E (2012) Histone modifications and lamin A regulate chromatin protein dynamics in early embryonic stem cell differentiation. Nat Commun 3:910. doi:10.1038/ncomms1915

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Meshorer E, Yellajoshula D, George E, Scambler PJ, Brown DT, Misteli T (2006) Hyperdynamic plasticity of chromatin proteins in pluripotent embryonic stem cells. Dev Cell 10(1):105–116

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Messerschmidt DM, Knowles BB, Solter D (2014) DNA methylation dynamics during epigenetic reprogramming in the germline and preimplantation embryos. Genes Dev 28(8):812–828. doi:10.1101/gad.234294.113

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mikkelsen TS, Ku M, Jaffe DB, Issac B, Lieberman E, Giannoukos G, Alvarez P, Brockman W, Kim TK, Koche RP, Lee W, Mendenhall E, O’Donovan A, Presser A, Russ C, Xie X, Meissner A, Wernig M, Jaenisch R, Nusbaum C, Lander ES, Bernstein BE (2007) Genome-wide maps of chromatin state in pluripotent and lineage-committed cells. Nature 448(7153):553–560. doi:10.1038/nature06008, nature06008 [pii]

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mikkelsen TS, Hanna J, Zhang X, Ku M, Wernig M, Schorderet P, Bernstein BE, Jaenisch R, Lander ES, Meissner A (2008) Dissecting direct reprogramming through integrative genomic analysis. Nature 454(7200):49–55. doi:10.1038/nature07056

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Montgomery RL, Davis CA, Potthoff MJ, Haberland M, Fielitz J, Qi X, Hill JA, Richardson JA, Olson EN (2007) Histone deacetylases 1 and 2 redundantly regulate cardiac morphogenesis, growth, and contractility. Genes Dev 21(14):1790–1802. doi:10.1101/gad.1563807

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Najm FJ, Chenoweth JG, Anderson PD, Nadeau JH, Redline RW, McKay RD, Tesar PJ (2011) Isolation of epiblast stem cells from preimplantation mouse embryos. Cell Stem Cell 8(3):318–325. doi:10.1016/j.stem.2011.01.016

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nakagawa M, Koyanagi M, Tanabe K, Takahashi K, Ichisaka T, Aoi T, Okita K, Mochiduki Y, Takizawa N, Yamanaka S (2008) Generation of induced pluripotent stem cells without Myc from mouse and human fibroblasts. Nat Biotechnol 26(1):101–106. doi:10.1038/nbt1374, nbt1374 [pii]

    Article  CAS  PubMed  Google Scholar 

  • Ochocki JD, Simon MC (2013) Nutrient-sensing pathways and metabolic regulation in stem cells. J Cell Biol 203(1):23–33. doi:10.1083/jcb.201303110

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Okano M, Bell DW, Haber DA, Li E (1999) DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development. Cell 99(3):247–257, S0092-8674(00)81656-6 [pii]

    Article  CAS  PubMed  Google Scholar 

  • Onder TT, Kara N, Cherry A, Sinha AU, Zhu N, Bernt KM, Cahan P, Marcarci BO, Unternaehrer J, Gupta PB, Lander ES, Armstrong SA, Daley GQ (2012) Chromatin-modifying enzymes as modulators of reprogramming. Nature 483(7391):598–602. doi:10.1038/nature10953

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pan G, Tian S, Nie J, Yang C, Ruotti V, Wei H, Jonsdottir GA, Stewart R, Thomson JA (2007) Whole-genome analysis of histone H3 lysine 4 and lysine 27 methylation in human embryonic stem cells. Cell Stem Cell 1(3):299–312. doi:10.1016/j.stem.2007.08.003, S1934-5909(07)00122-1 [pii]

    Article  CAS  PubMed  Google Scholar 

  • Pannetier M, Feil R (2007) Epigenetic stability of embryonic stem cells and developmental potential. Trends Biotechnol 25(12):556–562. doi:10.1016/j.tibtech.2007.09.003, S0167-7799(07)00261-2 [pii]

    Article  CAS  PubMed  Google Scholar 

  • Papp B, Plath K (2013) Epigenetics of reprogramming to induced pluripotency. Cell 152(6):1324–1343. doi:10.1016/j.cell.2013.02.043

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pauklin S, Vallier L (2013) The cell-cycle state of stem cells determines cell fate propensity. Cell 155(1):135–147. doi:10.1016/j.cell.2013.08.031

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Phillips-Cremins JE, Sauria ME, Sanyal A, Gerasimova TI, Lajoie BR, Bell JS, Ong CT, Hookway TA, Guo C, Sun Y, Bland MJ, Wagstaff W, Dalton S, McDevitt TC, Sen R, Dekker J, Taylor J, Corces VG (2013) Architectural protein subclasses shape 3D organization of genomes during lineage commitment. Cell 153(6):1281–1295. doi:10.1016/j.cell.2013.04.053

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Polo JM, Anderssen E, Walsh RM, Schwarz BA, Nefzger CM, Lim SM, Borkent M, Apostolou E, Alaei S, Cloutier J, Bar-Nur O, Cheloufi S, Stadtfeld M, Figueroa ME, Robinton D, Natesan S, Melnick A, Zhu J, Ramaswamy S, Hochedlinger K (2012) A molecular roadmap of reprogramming somatic cells into iPS cells. Cell 151(7):1617–1632. doi:10.1016/j.cell.2012.11.039

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Qin H, Diaz A, Blouin L, Lebbink RJ, Patena W, Tanbun P, LeProust EM, McManus MT, Song JS, Ramalho-Santos M (2014) Systematic identification of barriers to human iPSC generation. Cell 158(2):449–461. doi:10.1016/j.cell.2014.05.040

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rais Y, Zviran A, Geula S, Gafni O, Chomsky E, Viukov S, Mansour AA, Caspi I, Krupalnik V, Zerbib M, Maza I, Mor N, Baran D, Weinberger L, Jaitin DA, Lara-Astiaso D, Blecher-Gonen R, Shipony Z, Mukamel Z, Hagai T, Gilad S, Amann-Zalcenstein D, Tanay A, Amit I, Novershtern N, Hanna JH (2013) Deterministic direct reprogramming of somatic cells to pluripotency. Nature 502(7469):65–70. doi:10.1038/nature12587

    Article  CAS  PubMed  Google Scholar 

  • Reubinoff BE, Pera MF, Fong CY, Trounson A, Bongso A (2000) Embryonic stem cell lines from human blastocysts: somatic differentiation in vitro. Nat Biotechnol 18(4):399–404. doi:10.1038/74447

    Article  CAS  PubMed  Google Scholar 

  • Riising EM, Comet I, Leblanc B, Wu X, Johansen JV, Helin K (2014) Gene silencing triggers polycomb repressive complex 2 recruitment to CpG islands genome wide. Mol Cell 55(3):347–360. doi:10.1016/j.molcel.2014.06.005

    Article  CAS  PubMed  Google Scholar 

  • Ruiz S, Gore A, Li Z, Panopoulos AD, Montserrat N, Fung HL, Giorgetti A, Bilic J, Batchelder EM, Zaehres H, Scholer HR, Zhang K, Izpisua Belmonte JC (2013) Analysis of protein-coding mutations in hiPSCs and their possible role during somatic cell reprogramming. Nat Commun 4:1382. doi:10.1038/ncomms2381

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Samavarchi-Tehrani P, Golipour A, David L, Sung HK, Beyer TA, Datti A, Woltjen K, Nagy A, Wrana JL (2010) Functional genomics reveals a BMP-driven mesenchymal-to-epithelial transition in the initiation of somatic cell reprogramming. Cell Stem Cell 7(1):64–77. doi:10.1016/j.stem.2010.04.015

    Article  CAS  PubMed  Google Scholar 

  • Schmidt R, Plath K (2012) The roles of the reprogramming factors Oct4, Sox2 and Klf4 in resetting the somatic cell epigenome during induced pluripotent stem cell generation. Genome Biol 13(10):251. doi:10.1186/gb-2012-13-10-251

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schwabish MA, Struhl K (2004) Evidence for eviction and rapid deposition of histones upon transcriptional elongation by RNA polymerase II. Mol Cell Biol 24(23):10111–10117. doi:10.1128/MCB.24.23.10111-10117.2004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Segal E, Fondufe-Mittendorf Y, Chen L, Thastrom A, Field Y, Moore IK, Wang JP, Widom J (2006) A genomic code for nucleosome positioning. Nature 442(7104):772–778. doi:10.1038/nature04979

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sexton T, Yaffe E, Kenigsberg E, Bantignies F, Leblanc B, Hoichman M, Parrinello H, Tanay A, Cavalli G (2012) Three-dimensional folding and functional organization principles of the Drosophila genome. Cell 148(3):458–472. doi:10.1016/j.cell.2012.01.010

    Article  CAS  PubMed  Google Scholar 

  • Shipony Z, Mukamel Z, Cohen NM, Landan G, Chomsky E, Zeliger SR, Fried YC, Ainbinder E, Friedman N, Tanay A (2014) Dynamic and static maintenance of epigenetic memory in pluripotent and somatic cells. Nature. doi:10.1038/nature13458

    PubMed  Google Scholar 

  • Shirane K, Toh H, Kobayashi H, Miura F, Chiba H, Ito T, Kono T, Sasaki H (2013) Mouse oocyte methylomes at base resolution reveal genome-wide accumulation of non-CpG methylation and role of DNA methyltransferases. PLoS Genet 9(4):e1003439. doi:10.1371/journal.pgen.1003439

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shyh-Chang N, Locasale JW, Lyssiotis CA, Zheng Y, Teo RY, Ratanasirintrawoot S, Zhang J, Onder T, Unternaehrer JJ, Zhu H, Asara JM, Daley GQ, Cantley LC (2013) Influence of threonine metabolism on S-adenosylmethionine and histone methylation. Science 339(6116):222–226. doi:10.1126/science.1226603

    Article  PubMed  CAS  Google Scholar 

  • Smith ZD, Meissner A (2013) DNA methylation: roles in mammalian development. Nat Rev Genet 14(3):204–220. doi:10.1038/nrg3354

    Article  CAS  PubMed  Google Scholar 

  • Smith E, Shilatifard A (2010) The chromatin signaling pathway: diverse mechanisms of recruitment of histone-modifying enzymes and varied biological outcomes. Mol Cell 40(5):689–701. doi:10.1016/j.molcel.2010.11.031

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Smith ZD, Chan MM, Mikkelsen TS, Gu H, Gnirke A, Regev A, Meissner A (2012) A unique regulatory phase of DNA methylation in the early mammalian embryo. Nature 484(7394):339–344. doi:10.1038/nature10960

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Smith ZD, Chan MM, Humm KC, Karnik R, Mekhoubad S, Regev A, Eggan K, Meissner A (2014) DNA methylation dynamics of the human preimplantation embryo. Nature 511(7511):611–615. doi:10.1038/nature13581

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sridharan R, Tchieu J, Mason MJ, Yachechko R, Kuoy E, Horvath S, Zhou Q, Plath K (2009) Role of the murine reprogramming factors in the induction of pluripotency. Cell 136(2):364–377. doi:10.1016/j.cell.2009.01.001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Stadtfeld M, Apostolou E, Ferrari F, Choi J, Walsh RM, Chen T, Ooi SS, Kim SY, Bestor TH, Shioda T, Park PJ, Hochedlinger K (2012) Ascorbic acid prevents loss of Dlk1-Dio3 imprinting and facilitates generation of all-iPS cell mice from terminally differentiated B cells. Nat Genet 44(4):398–405, S391–392. doi:10.1038/ng.1110

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tada M, Tada T, Lefebvre L, Barton SC, Surani MA (1997) Embryonic germ cells induce epigenetic reprogramming of somatic nucleus in hybrid cells. EMBO J 16(21):6510–6520. doi:10.1093/emboj/16.21.6510

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Takahashi K, Yamanaka S (2006) Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126(4):663–676

    Article  CAS  PubMed  Google Scholar 

  • Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, Yamanaka S (2007) Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131(5):861–872. doi:10.1016/j.cell.2007.11.019, S0092-8674(07)01471-7 [pii]

    Article  CAS  PubMed  Google Scholar 

  • Takeuchi JK, Bruneau BG (2009) Directed transdifferentiation of mouse mesoderm to heart tissue by defined factors. Nature 459(7247):708–711. doi:10.1038/nature08039

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tee WW, Reinberg D (2014) Chromatin features and the epigenetic regulation of pluripotency states in ESCs. Development 141(12):2376–2390. doi:10.1242/dev.096982

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Teif VB, Vainshtein Y, Caudron-Herger M, Mallm JP, Marth C, Hofer T, Rippe K (2012) Genome-wide nucleosome positioning during embryonic stem cell development. Nat Struct Mol Biol 19(11):1185–1192. doi:10.1038/nsmb.2419

    Article  CAS  PubMed  Google Scholar 

  • Tesar PJ, Chenoweth JG, Brook FA, Davies TJ, Evans EP, Mack DL, Gardner RL, McKay RD (2007) New cell lines from mouse epiblast share defining features with human embryonic stem cells. Nature 448(7150):196–199. doi:10.1038/nature05972

    Article  CAS  PubMed  Google Scholar 

  • Theunissen TW, Powell BE, Wang H, Mitalipova M, Faddah DA, Reddy J, Fan ZP, Maetzel D, Ganz K, Shi L, Lungjangwa T, Imsoonthornruksa S, Stelzer Y, Rangarajan S, D’Alessio A, Zhang J, Gao Q, Dawlaty MM, Young RA, Gray NS, Jaenisch R (2014) Systematic identification of culture conditions for induction and maintenance of naive human pluripotency. Cell Stem Cell. doi:10.1016/j.stem.2014.07.002

    Google Scholar 

  • Thomson JA, Itskovitz-Eldor J, Shapiro SS, Waknitz MA, Swiergiel JJ, Marshall VS, Jones JM (1998) Embryonic stem cell lines derived from human blastocysts. Science 282(5391):1145–1147

    Article  CAS  PubMed  Google Scholar 

  • Tomizawa S, Kobayashi H, Watanabe T, Andrews S, Hata K, Kelsey G, Sasaki H (2011) Dynamic stage-specific changes in imprinted differentially methylated regions during early mammalian development and prevalence of non-CpG methylation in oocytes. Development 138(5):811–820. doi:10.1242/dev.061416

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Trivedi CM, Luo Y, Yin Z, Zhang M, Zhu W, Wang T, Floss T, Goettlicher M, Noppinger PR, Wurst W, Ferrari VA, Abrams CS, Gruber PJ, Epstein JA (2007) Hdac2 regulates the cardiac hypertrophic response by modulating Gsk3 beta activity. Nat Med 13(3):324–331. doi:10.1038/nm1552

    Article  CAS  PubMed  Google Scholar 

  • Tsumura A, Hayakawa T, Kumaki Y, Takebayashi S, Sakaue M, Matsuoka C, Shimotohno K, Ishikawa F, Li E, Ueda HR, Nakayama J, Okano M (2006) Maintenance of self-renewal ability of mouse embryonic stem cells in the absence of DNA methyltransferases Dnmt1, Dnmt3a and Dnmt3b. Genes Cells 11(7):805–814. doi:10.1111/j.1365-2443.2006.00984.x, GTC984 [pii]

    Article  CAS  PubMed  Google Scholar 

  • Wang Z, Zang C, Cui K, Schones DE, Barski A, Peng W, Zhao K (2009) Genome-wide mapping of HATs and HDACs reveals distinct functions in active and inactive genes. Cell 138(5):1019–1031. doi:10.1016/j.cell.2009.06.049

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ware CB, Wang L, Mecham BH, Shen L, Nelson AM, Bar M, Lamba DA, Dauphin DS, Buckingham B, Askari B, Lim R, Tewari M, Gartler SM, Issa JP, Pavlidis P, Duan Z, Blau CA (2009) Histone deacetylase inhibition elicits an evolutionarily conserved self-renewal program in embryonic stem cells. Cell Stem Cell 4(4):359–369. doi:10.1016/j.stem.2009.03.001, S1934-5909(09)00102-7 [pii]

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wei Z, Gao F, Kim S, Yang H, Lyu J, An W, Wang K, Lu W (2013) Klf4 organizes long-range chromosomal interactions with the oct4 locus in reprogramming and pluripotency. Cell Stem Cell 13(1):36–47. doi:10.1016/j.stem.2013.05.010

    Article  CAS  PubMed  Google Scholar 

  • Weissbein U, Benvenisty N, Ben-David U (2014) Quality control: genome maintenance in pluripotent stem cells. J Cell Biol 204(2):153–163. doi:10.1083/jcb.201310135

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wernig M, Meissner A, Cassady JP, Jaenisch R (2008) c-Myc is dispensable for direct reprogramming of mouse fibroblasts. Cell Stem Cell 2(1):10–12. doi:10.1016/j.stem.2007.12.001

    Article  CAS  PubMed  Google Scholar 

  • Whyte WA, Orlando DA, Hnisz D, Abraham BJ, Lin CY, Kagey MH, Rahl PB, Lee TI, Young RA (2013) Master transcription factors and mediator establish super-enhancers at key cell identity genes. Cell 153(2):307–319. doi:10.1016/j.cell.2013.03.035

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Williams K, Christensen J, Pedersen MT, Johansen JV, Cloos PA, Rappsilber J, Helin K (2011) TET1 and hydroxymethylcytosine in transcription and DNA methylation fidelity. Nature 473(7347):343–348. doi:10.1038/nature10066

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Woodcock CL, Skoultchi AI, Fan Y (2006) Role of linker histone in chromatin structure and function: H1 stoichiometry and nucleosome repeat length. Chromosome Res 14(1):17–25

    Article  CAS  PubMed  Google Scholar 

  • Wu H, Zhang Y (2014) Reversing DNA methylation: mechanisms, genomics, and biological functions. Cell 156(1–2):45–68. doi:10.1016/j.cell.2013.12.019

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wu H, D’Alessio AC, Ito S, Wang Z, Cui K, Zhao K, Sun YE, Zhang Y (2011) Genome-wide analysis of 5-hydroxymethylcytosine distribution reveals its dual function in transcriptional regulation in mouse embryonic stem cells. Genes Dev 25(7):679–684. doi:10.1101/gad.2036011

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xie W, Barr CL, Kim A, Yue F, Lee AY, Eubanks J, Dempster EL, Ren B (2012) Base-resolution analyses of sequence and parent-of-origin dependent DNA methylation in the mouse genome. Cell 148(4):816–831. doi:10.1016/j.cell.2011.12.035

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xie W, Schultz MD, Lister R, Hou Z, Rajagopal N, Ray P, Whitaker JW, Tian S, Hawkins RD, Leung D, Yang H, Wang T, Lee AY, Swanson SA, Zhang J, Zhu Y, Kim A, Nery JR, Urich MA, Kuan S, Yen CA, Klugman S, Yu P, Suknuntha K, Propson NE, Chen H, Edsall LE, Wagner U, Li Y, Ye Z, Kulkarni A, Xuan Z, Chung WY, Chi NC, Antosiewicz-Bourget JE, Slukvin I, Stewart R, Zhang MQ, Wang W, Thomson JA, Ecker JR, Ren B (2013) Epigenomic analysis of multilineage differentiation of human embryonic stem cells. Cell 153(5):1134–1148. doi:10.1016/j.cell.2013.04.022

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xu C, Inokuma MS, Denham J, Golds K, Kundu P, Gold JD, Carpenter MK (2001) Feeder-free growth of undifferentiated human embryonic stem cells. Nat Biotechnol 19(10):971–974. doi:10.1038/nbt1001-971

    Article  CAS  PubMed  Google Scholar 

  • Xue Y, Wong J, Moreno GT, Young MK, Cote J, Wang W (1998) NURD, a novel complex with both ATP-dependent chromatin-remodeling and histone deacetylase activities. Mol Cell 2(6):851–861

    Article  CAS  PubMed  Google Scholar 

  • Yamaguchi S, Hong K, Liu R, Shen L, Inoue A, Diep D, Zhang K, Zhang Y (2012) Tet1 controls meiosis by regulating meiotic gene expression. Nature 492(7429):443–447. doi:10.1038/nature11709

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yamaguchi S, Shen L, Liu Y, Sendler D, Zhang Y (2013) Role of Tet1 in erasure of genomic imprinting. Nature 504(7480):460–464. doi:10.1038/nature12805

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yan Z, Wang Z, Sharova L, Sharov AA, Ling C, Piao Y, Aiba K, Matoba R, Wang W, Ko MS (2008) BAF250B-associated SWI/SNF chromatin-remodeling complex is required to maintain undifferentiated mouse embryonic stem cells. Stem Cells 26(5):1155–1165. doi:10.1634/stemcells.2007-0846, 2007–0846 [pii]

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yanes O, Clark J, Wong DM, Patti GJ, Sanchez-Ruiz A, Benton HP, Trauger SA, Desponts C, Ding S, Siuzdak G (2010) Metabolic oxidation regulates embryonic stem cell differentiation. Nat Chem Biol 6(6):411–417. doi:10.1038/nchembio.364

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ying QL, Wray J, Nichols J, Batlle-Morera L, Doble B, Woodgett J, Cohen P, Smith A (2008) The ground state of embryonic stem cell self-renewal. Nature 453(7194):519–523. doi:10.1038/nature06968, nature06968 [pii]

    Article  CAS  PubMed  Google Scholar 

  • You A, Tong JK, Grozinger CM, Schreiber SL (2001) CoREST is an integral component of the CoREST-human histone deacetylase complex. Proc Natl Acad Sci USA 98(4):1454–1458. doi:10.1073/pnas.98.4.1454

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Young RA (2011) Control of the embryonic stem cell state. Cell 144(6):940–954. doi:10.1016/j.cell.2011.01.032

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yu J, Vodyanik MA, Smuga-Otto K, Antosiewicz-Bourget J, Frane JL, Tian S, Nie J, Jonsdottir GA, Ruotti V, Stewart R, Slukvin II, Thomson JA (2007) Induced pluripotent stem cell lines derived from human somatic cells. Science 318(5858):1917–1920. doi:10.1126/science.1151526, 1151526 [pii]

    Article  CAS  PubMed  Google Scholar 

  • Zhang X, Bolt M, Guertin MJ, Chen W, Zhang S, Cherrington BD, Slade DJ, Dreyton CJ, Subramanian V, Bicker KL, Thompson PR, Mancini MA, Lis JT, Coonrod SA (2012) Peptidylarginine deiminase 2-catalyzed histone H3 arginine 26 citrullination facilitates estrogen receptor alpha target gene activation. Proc Natl Acad Sci USA 109(33):13331–13336. doi:10.1073/pnas.1203280109

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhou Q, Melton DA (2008) Extreme makeover: converting one cell into another. Cell Stem Cell 3(4):382–388. doi:10.1016/j.stem.2008.09.015

    Article  CAS  PubMed  Google Scholar 

  • Zhou Q, Brown J, Kanarek A, Rajagopal J, Melton DA (2008) In vivo reprogramming of adult pancreatic exocrine cells to beta-cells. Nature 455(7213):627–632. doi:10.1038/nature07314

    Article  CAS  PubMed  Google Scholar 

  • Zimmermann S, Kiefer F, Prudenziati M, Spiller C, Hansen J, Floss T, Wurst W, Minucci S, Gottlicher M (2007) Reduced body size and decreased intestinal tumor rates in HDAC2-mutant mice. Cancer Res 67(19):9047–9054. doi:10.1158/0008-5472.CAN-07-0312

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Eran Meshorer .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Salts, N., Meshorer, E. (2016). Epigenetics in Development, Differentiation and Reprogramming. In: Bazett-Jones, D., Dellaire, G. (eds) The Functional Nucleus. Springer, Cham. https://doi.org/10.1007/978-3-319-38882-3_18

Download citation

Publish with us

Policies and ethics