Stem cells, including pluripotent embryonic stem (ES) cells and lineage-restricted adult stem cells, share a capacity to self-renew and generate differentiated progeny. Analysis of their epigenetic properties can help us to understand the molecular mechanism that underlies this important property.
Data from different approaches, including fluorescent recovery after photobleaching (FRAP) and replication timing analysis, have suggested that the chromatin of ES cells is generally less compact and more 'permissive' than that of normal cells.
Promoters of many non-transcribed developmental regulator genes share an unusual 'bivalent' chromatin pattern in ES cells, whereby histone modifications that are normally associated with gene transcription (acetylation at lysine 9 and trimethylation at lysine 4 of histone H3) co-exist with trimethylation at lysine 27 of histone H3, which is usually found at repressed loci.
These bivalent patterns are thought to keep non-transcribed genes in a 'poised' conformation, ready for expression in response to developmental cues.
Trimethylation of histone H3 lysine 27 is created by Polycomb repressive complex 2 (PRC2), which in turn provides a binding site for PRC1. Consistently, ES cells that are mutant for Polycomb components show derepression of several tissue-specific genes that carry bivalent chromatin marks in wild-type cells.
Polycomb complexes are ubiquitously expressed, whereas bivalent chromatin is unusual and is not thought to be commonly found in differentiated cells.
Genome-wide studies indicate that Polycomb target genes in ES cells are often co-occupied by a 'triad' of pluripotency-associated transcription factors: OCT4, SOX2 and NANOG. This suggests that these factors might have a role in recruiting Polycomb complexes to target promoters, possibly along with chromatin modifiers with an opposing function (such as histone acetyltransferases). However, many Polycomb targets in ES cells do not bind the regulatory 'triad', indicating that our knowledge of these events remains preliminary.
Polycomb complexes are also important for the maintenance of adult stem-cell populations. Whether they create bivalent chromatin in this context remains to be found.
Pluripotent stem cells, similar to more restricted stem cells, are able to both self-renew and generate differentiated progeny. Although this dual functionality has been much studied, the search for molecular signatures of 'stemness' and pluripotency is only now beginning to gather momentum. While the focus of much of this work has been on the transcriptional features of embryonic stem cells, recent studies have indicated the importance of unique epigenetic profiles that keep key developmental genes 'poised' in a repressed but activatable state. Determining how these epigenetic features relate to the transcriptional signatures of ES cells, and whether they are also important in other types of stem cell, is a key challenge for the future.
This is a preview of subscription content, access via your institution
Open Access articles citing this article.
Cellular and Molecular Life Sciences Open Access 19 August 2021
Long noncoding RNA CCDC144NL-AS1 knockdown induces naïve-like state conversion of human pluripotent stem cells
Stem Cell Research & Therapy Open Access 29 July 2019
Methylation and PTEN activation in dental pulp mesenchymal stem cells promotes osteogenesis and reduces oncogenesis
Nature Communications Open Access 20 May 2019
Subscribe to Journal
Get full journal access for 1 year
only $6.58 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Tax calculation will be finalised during checkout.
Get time limited or full article access on ReadCube.
All prices are NET prices.
Chambers, I. & Smith, A. Self-renewal of teratocarcinoma and embryonic stem cells. Oncogene 23, 7150–7160 (2004).
Keller, G. Embryonic stem cell differentiation: emergence of a new era in biology and medicine. Genes Dev. 19, 1129–1155 (2005).
Smith, A. G. Embryo-derived stem cells: of mice and men. Annu. Rev. Cell Dev. Biol. 17, 435–462 (2001).
Lovell-Badge, R. The future for stem cell research. Nature 414, 88–91 (2001).
Pessina, A. & Gribaldo, L. The key role of adult stem cells: therapeutic perspectives. Curr. Med. Res. Opin. 22, 2287–2300 (2006).
Johnson, B. V., Rathjen, J. & Rathjen, P. D. Transcriptional control of pluripotency: decisions in early development. Curr. Opin. Genet. Dev. 16, 447–454 (2006).
Noggle, S. A., James, D. & Brivanlou, A. H. A molecular basis for human embryonic stem cell pluripotency. Stem Cell Rev. 1, 111–118 (2005).
Chambers, I. The molecular basis of pluripotency in mouse embryonic stem cells. Cloning Stem Cells 6, 386–391 (2004).
Evans, M. J. & Kaufman, M. H. Establishment in culture of pluripotential cells from mouse embryos. Nature 292, 154–156 (1981).
Shamblott, M. J. et al. Derivation of pluripotent stem cells from cultured human primordial germ cells. Proc. Natl Acad. Sci. USA 95, 13726–13731 (1998).
McLaren, A. & Durcova-Hills, G. Germ cells and pluripotent stem cells in the mouse. Reprod. Fertil. Dev. 13, 661–664 (2001).
Kubota, H. & Brinster, R. L. Technology insight: in vitro culture of spermatogonial stem cells and their potential therapeutic uses. Nature Clin. Pract. Endocrinol. Metab. 2, 99–108 (2006).
Nagano, M. et al. Transgenic mice produced by retroviral transduction of male germ-line stem cells. Proc. Natl Acad. Sci. USA 98, 13090–13095 (2001).
Niwa, H., Burdon, T., Chambers, I. & Smith, A. Self-renewal of pluripotent embryonic stem cells is mediated via activation of STAT3. Genes Dev. 12, 2048–2060 (1998).
Tada, M., Takahama, Y., Abe, K., Nakatsuji, N. & Tada, T. Nuclear reprogramming of somatic cells by in vitro hybridization with ES cells. Curr. Biol. 11, 1553–1558 (2001).
Tada, M., Tada, T., Lefebvre, L., Barton, S. C. & Surani, M. A. Embryonic germ cells induce epigenetic reprogramming of somatic nucleus in hybrid cells. EMBO J. 16, 6510–6520 (1997).
Ramalho-Santos, M., Yoon, S., Matsuzaki, Y., Mulligan, R. C. & Melton, D. A. 'Stemness': transcriptional profiling of embryonic and adult stem cells. Science 298, 597–600 (2002).
Ivanova, N. B. et al. A stem cell molecular signature. Science 298, 601–604 (2002).
Conti, L., Reitano, E. & Cattaneo, E. Neural stem cell systems: diversities and properties after transplantation in animal models of diseases. Brain Pathol. 16, 143–154 (2006).
Fortunel, N. O. et al. Comment on 'Stemness': transcriptional profiling of embryonic and adult stem cells' and 'A stem cell molecular signature'. Science 302, 393 (2003).
Sato, N. et al. Molecular signature of human embryonic stem cells and its comparison with the mouse. Dev. Biol. 260, 404–413 (2003).
Sperger, J. M. et al. Gene expression patterns in human embryonic stem cells and human pluripotent germ cell tumors. Proc. Natl Acad. Sci. USA 100, 13350–13355 (2003).
Bhattacharya, B. et al. Gene expression in human embryonic stem cell lines: unique molecular signature. Blood 103, 2956–2964 (2004).
Ginis, I. et al. Differences between human and mouse embryonic stem cells. Dev. Biol. 269, 360–380 (2004).
Evsikov, A. V. & Solter, D. Comment on 'Stemness': transcriptional profiling of embryonic and adult stem cells' and 'A stem cell molecular signature'. Science 302, 393 (2003).
Ivanova, N. B. et al. Response to Comments on 'Stemness': transcriptional profiling of embryonic and adult stem cells' and 'A stem cell molecular signature'. Science 302, 393 (2002).
Mikkers, H. & Frisen, J. Deconstructing stemness. EMBO J. 24, 2715–2719 (2005).
Pritsker, M., Doniger, T. T., Kramer, L. C., Westcot, S. E. & Lemischka, I. R. Diversification of stem cell molecular repertoire by alternative splicing. Proc. Natl Acad. Sci. USA 102, 14290–14295 (2005).
Reik, W., Dean, W. & Walter, J. Epigenetic reprogramming in mammalian development. Science 293, 1089–1093 (2001).
Jenuwein, T. & Allis, C. D. Translating the histone code. Science 293, 1074–1080 (2001).
Bernstein, E. & Allis, C. D. RNA meets chromatin. Genes Dev. 19, 1635–1655 (2005).
Saha, A., Wittmeyer, J. & Cairns, B. R. Chromatin remodelling: the industrial revolution of DNA around histones. Nature Rev. Mol. Cell Biol. 7, 437–447 (2006).
Mostoslavsky, R., Alt, F. W. & Bassing, C. H. Chromatin dynamics and locus accessibility in the immune system. Nature Immunol. 4, 603–606 (2003).
Donaldson, A. D. Shaping time: chromatin structure and the DNA replication programme. Trends Genet. 21, 444–449 (2005).
Williams, R. R. & Fisher, A. G. Chromosomes, positions please! Nature Cell Biol. 5, 388–390 (2003).
Jaenisch, R. & Bird, A. Epigenetic regulation of gene expression: how the genome integrates intrinsic and environmental signals. Nature Genet. 33, S245–S254 (2003).
Henikoff, S., Furuyama, T. & Ahmad, K. Histone variants, nucleosome assembly and epigenetic inheritance. Trends Genet. 20, 320–326 (2004).
Nakatani, Y., Tagami, H. & Shestakova, E. How is epigenetic information on chromatin inherited after DNA replication? Ernst Schering Res. Found. Workshop 57, 89–96 (2006).
Richards, E. J. Inherited epigenetic variation — revisiting soft inheritance. Nature Rev. Genet. 7, 395–401 (2006).
Smale, S. T. The establishment and maintenance of lymphocyte identity through gene silencing. Nature Immunol. 4, 607–615 (2003).
Lyko, F., Beisel, C., Marhold, J. & Paro, R. Epigenetic regulation in Drosophila. Curr. Top. Microbiol. Immunol. 310, 23–44 (2006).
Ringrose, L. & Paro, R. Epigenetic regulation of cellular memory by the Polycomb and Trithorax group proteins. Annu. Rev. Genet. 38, 413–443 (2004).
Arney, K. L. & Fisher, A. G. Epigenetic aspects of differentiation. J. Cell Sci. 117, 4355–4363 (2004).
Wiblin, A. E., Cui, W., Clark, A. J. & Bickmore, W. A. Distinctive nuclear organisation of centromeres and regions involved in pluripotency in human embryonic stem cells. J. Cell Sci. 118, 3861–3868 (2005).
Williams, R. R. et al. Neural induction promotes large-scale chromatin reorganisation of the Mash1 locus. J. Cell Sci. 119, 132–140 (2006).
Meshorer, E. et al. Hyperdynamic plasticity of chromatin proteins in pluripotent embryonic stem cells. Dev. Cell 10, 105–116 (2006). This study uses FRAP to analyse the mobility of chromatin proteins in ES cells versus differentiated cells.
Keohane, A. M., O'Neill, L. P., Belyaev, N. D., Lavender, J. S. & Turner, B. M. X-inactivation and histone H4 acetylation in embryonic stem cells. Dev. Biol. 180, 618–630 (1996).
Brown, K. E., Baxter, J., Graf, D., Merkenschlager, M. & Fisher, A. G. Dynamic repositioning of genes in the nucleus of lymphocytes preparing for cell division. Mol. Cell 3, 207–217 (1999).
Brown, K. E. et al. Association of transcriptionally silent genes with Ikaros complexes at centromeric heterochromatin. Cell 91, 845–854 (1997).
Su, R. C. et al. Dynamic assembly of silent chromatin during thymocyte maturation. Nature Genet. 36, 502–506 (2004).
Phair, R. D., Gorski, S. A. & Misteli, T. Measurement of dynamic protein binding to chromatin in vivo, using photobleaching microscopy. Methods Enzymol. 375, 393–414 (2004).
Brown, D. T. Histone H1 and the dynamic regulation of chromatin function. Biochem. Cell Biol. 81, 221–227 (2003).
Phair, R. D. et al. Global nature of dynamic protein–chromatin interactions in vivo: three-dimensional genome scanning and dynamic interaction networks of chromatin proteins. Mol. Cell. Biol. 24, 6393–6402 (2004).
Perry, P. et al. A dynamic switch in the replication timing of key regulator genes in embryonic stem cells upon neural induction. Cell Cycle 3, 1645–1650 (2004).
Hiratani, I., Leskovar, A. & Gilbert, D. M. Differentiation-induced replication-timing changes are restricted to AT-rich/long interspersed nuclear element (LINE)-rich isochores. Proc. Natl Acad. Sci. USA 101, 16861–16866 (2004). References 54 and 55 demonstrate that developmental genes alter their replication timing upon ES differentiation into neural progenitors.
Schubeler, D. et al. Genome-wide DNA replication profile for Drosophila melanogaster: a link between transcription and replication timing. Nature Genet. 32, 438–442 (2002).
Azuara, V. et al. Heritable gene silencing in lymphocytes delays chromatid resolution without affecting the timing of DNA replication. Nature Cell Biol. 5, 668–674 (2003).
Lin, C. M., Fu, H., Martinovsky, M., Bouhassira, E. & Aladjem, M. I. Dynamic alterations of replication timing in mammalian cells. Curr. Biol. 13, 1019–1028 (2003).
Simon, I. et al. Developmental regulation of DNA replication timing at the human β-globin locus. EMBO J. 20, 6150–6157 (2001).
Vogelauer, M., Rubbi, L., Lucas, I., Brewer, B. J. & Grunstein, M. Histone acetylation regulates the time of replication origin firing. Mol. Cell 10, 1223–1233 (2002).
Aparicio, J. G., Viggiani, C. J., Gibson, D. G. & Aparicio, O. M. The Rpd3–Sin3 histone deacetylase regulates replication timing and enables intra-S origin control in Saccharomyces cerevisiae. Mol. Cell. Biol. 24, 4769–4780 (2004).
Azuara, V. et al. Chromatin signatures of pluripotent cell lines. Nature Cell Biol. 8, 532–538 (2006). This study shows that in mouse ES cells, but not in differentiated cells, many non-transcribed developmental genes replicate early in S phase and have bivalent chromatin profiles.
Chaumeil, J., Okamoto, I., Guggiari, M. & Heard, E. Integrated kinetics of X chromosome inactivation in differentiating embryonic stem cells. Cytogenet. Genome Res. 99, 75–84 (2002).
Bernstein, B. E. et al. A bivalent chromatin structure marks key developmental genes in embryonic stem cells. Cell 125, 315–326 (2006). This study identifies bivalent chromatin profiles in mouse ES cells using high-resolution ChIP-on-chip analysis.
Chambeyron, S., Da Silva, N. R., Lawson, K. A. & Bickmore, W. A. Nuclear re-organisation of the HOXB complex during mouse embryonic development. Development 132, 2215–2223 (2005).
Szutorisz, H. et al. Formation of an active tissue-specific chromatin domain initiated by epigenetic marking at the embryonic stem cell stage. Mol. Cell. Biol. 25, 1804–1820 (2005).
Lee, T. I. et al. Control of developmental regulators by Polycomb in human embryonic stem cells. Cell 125, 301–313 (2006).
Bracken, A. P., Dietrich, N., Pasini, D., Hansen, K. H. & Helin, K. Genome-wide mapping of Polycomb target genes unravels their roles in cell fate transitions. Genes Dev. 20, 1123–1136 (2006).
Boyer, L. A. et al. Polycomb complexes repress developmental regulators in murine embryonic stem cells. Nature 441, 349–353 (2006). References 67 and 69 show that PcG complexes occupy promoters of repressed developmental genes in human and mouse ES cells.
Schwartz, Y. B. et al. Genome-wide analysis of Polycomb targets in Drosophila melanogaster. Nature Genet. 38, 700–705 (2006).
Negre, N. et al. Chromosomal distribution of PcG proteins during Drosophila development. PLoS Biol. 4, e170 (2006).
Tolhuis, B. et al. Genome-wide profiling of PRC1 and PRC2 Polycomb chromatin binding in Drosophila melanogaster. Nature Genet. 38, 694–699 (2006).
Jorgensen, H. F. et al. Stem cells primed for action: polycomb repressive complexes restrain the expression of lineage-specific regulators in embryonic stem cells. Cell Cycle 5, 1411–1414 (2006).
Pera, M. F. & Trounson, A. O. Human embryonic stem cells: prospects for development. Development 131, 5515–5525 (2004).
Schwartz, Y. B. & Pirrotta, V. Polycomb silencing mechanisms and the management of genomic programmes. Nature Rev. Genet. 8, 9–22 (2007).
Cao, R., Tsukada, Y. & Zhang, Y. Role of Bmi-1 and Ring1A in H2A ubiquitylation and Hox gene silencing. Mol. Cell 20, 845–854 (2005).
de Napoles, M. et al. Polycomb group proteins Ring1A/B link ubiquitylation of histone H2A to heritable gene silencing and X inactivation. Dev. Cell 7, 663–676 (2004).
Wang, H. et al. Role of histone H2A ubiquitination in Polycomb silencing. Nature 431, 873–878 (2004).
Schoeftner, S. et al. Recruitment of PRC1 function at the initiation of X inactivation independent of PRC2 and silencing. EMBO J. 25, 3110–3122 (2006).
Min, J., Zhang, Y. & Xu, R. M. Structural basis for specific binding of Polycomb chromodomain to histone H3 methylated at Lys 27. Genes Dev. 17, 1823–1828 (2003).
Dellino, G. I. et al. Polycomb silencing blocks transcription initiation. Mol. Cell 13, 887–893 (2004).
Wang, L. et al. Hierarchical recruitment of polycomb group silencing complexes. Mol. Cell 14, 637–646 (2004).
Mohd-Sarip, A. et al. Architecture of a Polycomb nucleoprotein complex. Mol. Cell 24, 91–100 (2006).
Zhang, H. et al. The C. elegans Polycomb gene SOP-2 encodes an RNA binding protein. Mol. Cell 14, 841–847 (2004).
Kim, D. H., Villeneuve, L. M., Morris, K. V. & Rossi, J. J. Argonaute-1 directs siRNA-mediated transcriptional gene silencing in human cells. Nature Struct. Mol. Biol. 13, 793–797 (2006).
Vire, E. et al. The Polycomb group protein EZH2 directly controls DNA methylation. Nature 439, 871–874 (2006).
Widschwendter, M. et al. Epigenetic stem cell signature in cancer. Nature Genet. 39, 157–158 (2007).
Ohm, J. et al. A stem cell-like chromatin pattern may predispose tumor suppressor genes to DNA hypermethylation and heritable silencing. Nature Genet. 39, 237–242 (2007).
Schlesinger, Y. et al. Polycomb-mediated methylation on Lys27 of histone H3 pre-marks genes for de novo methylation in cancer. Nature Genet. 39, 232–236 (2007).
Boyer, L. A. et al. Core transcriptional regulatory circuitry in human embryonic stem cells. Cell 122, 947–956 (2005).
Loh, Y. H. et al. The Oct4 and Nanog transcription network regulates pluripotency in mouse embryonic stem cells. Nature Genet. 38, 431–440 (2006). References 90 and 91 show that key regulator genes Oct4 and Nanog bind activated as well as repressed developmental targets in human and mouse ES cells.
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 121, 645–657 (2005).
Takahashi, K. & Yamanaka, S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126, 663–676 (2006).
Pritsker, M., Ford, N. R., Jenq, H. T. & Lemischka, I. R. Genomewide gain-of-function genetic screen identifies functionally active genes in mouse embryonic stem cells. Proc. Natl Acad. Sci. USA 103, 6946–6951 (2006).
Gong, Y. et al. NSPc1 is a cell growth regulator that acts as a transcriptional repressor of p21Waf1/Cip1 via the RARE element. Nucleic Acids Res. 34, 6158–6169 (2006).
Ivanova, N. et al. Dissecting self-renewal in stem cells with RNA interference. Nature 442, 533–538 (2006).
Parrish, J. R., Gulyas, K. D. & Finley, R. L. Jr . Yeast two-hybrid contributions to interactome mapping. Curr. Opin. Biotechnol. 17, 387–393 (2006).
Wang, J. et al. A protein interaction network for pluripotency of embryonic stem cells. Nature 444, 364–368 (2006).
O'Neill, L. P., VerMilyea, M. D. & Turner, B. M. Epigenetic characterization of the early embryo with a chromatin immunoprecipitation protocol applicable to small cell populations. Nature Genet. 38, 835–841 (2006).
Dzierzak, E. The emergence of definitive hematopoietic stem cells in the mammal. Curr. Opin. Hematol. 12, 197–202 (2005).
Park, I. K. et al. BMI-1 is required for maintenance of adult self-renewing haematopoietic stem cells. Nature 423, 302–305 (2003).
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. 19, 1432–1437 (2005).
Jacobs, J. J., Kieboom, K., Marino, S., DePinho, R. A. & van Lohuizen, M. The oncogene and Polycomb-group gene bmi-1 regulates cell proliferation and senescence through the ink4a locus. Nature 397, 164–168 (1999).
Jacobs, J. J. et al. Bmi-1 collaborates with c-Myc in tumorigenesis by inhibiting c-Myc-induced apoptosis via INK4a/ARF. Genes Dev. 13, 2678–2690 (1999).
Molofsky, A. V. et al. Bmi-1 dependence distinguishes neural stem cell self-renewal from progenitor proliferation. Nature 425, 962–967 (2003).
Chagraoui, J. et al. E4F1: a novel candidate factor for mediating BMI1 function in primitive hematopoietic cells. Genes Dev. 20, 2110–2120 (2006).
Fischle, W., Wang, Y. & Allis, C. D. Histone and chromatin cross-talk. Curr. Opin. Cell Biol. 15, 172–183 (2003).
Jones, P. L. et al. Methylated DNA and MeCP2 recruit histone deacetylase to repress transcription. Nature Genet. 19, 187–191 (1998).
Nan, X. et al. Transcriptional repression by the methyl-CpG-binding protein MeCP2 involves a histone deacetylase complex. Nature 393, 386–389 (1998).
Li, E. Chromatin modification and epigenetic reprogramming in mammalian development. Nature Rev. Genet. 3, 662–673 (2002).
Lyko, F. DNA methylation learns to fly. Trends Genet. 17, 169–172 (2001).
Richards, E. J. & Elgin, S. C. Epigenetic codes for heterochromatin formation and silencing: rounding up the usual suspects. Cell 108, 489–500 (2002).
Zhang, J., Xu, F., Hashimshony, T., Keshet, I. & Cedar, H. Establishment of transcriptional competence in early and late S phase. Nature 420, 198–202 (2002).
McNairn, A. J. & Gilbert, D. M. Epigenomic replication: linking epigenetics to DNA replication. BioEssays 25, 647–656 (2003).
Orlando, V. Mapping chromosomal proteins in vivo by formaldehyde-crosslinked-chromatin immunoprecipitation. Trends Biochem. Sci. 25, 99–104 (2000).
Buck, M. J. & Lieb, J. D. ChIP-chip: considerations for the design, analysis, and application of genome-wide chromatin immunoprecipitation experiments. Genomics 83, 349–360 (2004).
Negre, N., Lavrov, S., Hennetin, J., Bellis, M. & Cavalli, G. Mapping the distribution of chromatin proteins by ChIP on chip. Methods Enzymol. 410, 316–341 (2006).
Wei, C. L. et al. A global map of p53 transcription-factor binding sites in the human genome. Cell 124, 207–219 (2006).
Gilbert, N. et al. DNA methylation affects nuclear organisation, histone modifications and linker histone binding but not chromatin compaction. J. Cell Biol. (in the press).
M.S. and A.G.F. thank the Medical Research Council UK for continued support.
The authors declare no competing financial interests.
Describes cells that can, in theory, differentiate into every cell type of the adult organism.
- Lineage restriction
The narrowing down of a range of differentiation pathways that a cell is able to follow.
- Polycomb group proteins
A group of transcriptional repressors that are required to maintain the inactive state of genes during development. Polycomb proteins are known to modify the chromatin structure around their binding sites, which include the promoters of many developmental regulator genes.
- Inner cell mass
A small clump of apparently undifferentiated cells in the blastocyst, which gives rise to the entire fetus and some of its extraembryonic membranes.
An early stage of mammalian embryonic development at which the first cell lineages become established.
- Primordial germ layer
An embryonic layer that will give rise to gametes in the adult organism.
- DNA methylation
An epigenetically propagated covalent modification of DNA that, in mammals, occurs at cytosine deoxynucleotides. DNA methylation is thought to inhibit transcription, both by preventing transcription-factor binding to DNA and through interactions with methyl-CpG-binding proteins that recruit histone-modifying and chromatin-remodelling factors.
- Small interfering RNAs
(siRNAs). Small antisense RNAs (20–25 nucleotides long) that are generated from specific dsRNAs. siRNAs trigger RNAi pathways, which negatively regulate gene expression by post-transcriptional mechanisms.
- Constitutive heterochromatin
Areas of inactive chromatin that remain condensed in all tissue types. It is usually found at chromosomal regions that contain a high density of repetitive DNA elements, such as centromeres and telomeres.
- Fluorescent recovery after photobleaching
A microscopy-based technique that is used to measure the movement (for example, diffusion rates) of fluorescently tagged molecules (usually proteins) over time in vivo. Specific regions in a cell are irreversibly photobleached using a laser. Over time, fluorescence is usually restored as unbleached molecules diffuse into the bleached area. The recovery time can be used as a measure of protein mobility.
- Embryonic carcinoma cells
Cell lines that are derived from tumours that arise from transplantation of early-stage embryos to immunologically compatible animals. These cells can differentiate into many tissue types, and studies using them have pioneered stem-cell research. However, embryonic carcinoma cells have a significantly more restricted lineage potential than ES cells and show a high degree of variation depending on a cell line.
- Carrier ChIP
A chromatin immunoprecipitation technique that uses carrier DNA to allow small amounts of starting material to be analysed.
About this article
Cite this article
Spivakov, M., Fisher, A. Epigenetic signatures of stem-cell identity. Nat Rev Genet 8, 263–271 (2007). https://doi.org/10.1038/nrg2046
This article is cited by
Cellular and Molecular Life Sciences (2021)
Journal of Assisted Reproduction and Genetics (2020)
Long noncoding RNA CCDC144NL-AS1 knockdown induces naïve-like state conversion of human pluripotent stem cells
Stem Cell Research & Therapy (2019)
Uncoupling of in-vitro identity of embryonic limb derived skeletal progenitors and their in-vivo bone forming potential
Scientific Reports (2019)