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Frontiers in Biology

Front. Biol.    2016, Vol. 11 Issue (2) : 65-74     DOI: 10.1007/s11515-016-1399-x
Function of Polycomb repressive complexes in stem cells
Jin He()
Department of Biochemistry and Molecular Biology, College of Natural Science, Michigan State University, East Lansing, MI 48824, USA
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Stem cells are unique cell populations identified in a variety of normal tissues and some cancers. Maintenance of stem cell pools is essential for normal development, tissue homeostasis, and tumorigenesis. Recent studies have revealed that Polycomb repressive complexes (PRCs) play a central role in maintaining stem cells by repressing cellular senescence and differentiation. Here, we will review recent findings on dynamic composition of PRC complexes and sub-complexes, how PRCs are recruited to chromatin, and their functional roles in maintaining self-renewal of stem cells. Furthermore, we will discuss how PRCs, CpG islands (CGIs), the INK4A/ARF/INK4B locus, and developmental genes form a hierarchical regulatory axis that is utilized by a variety of stem cells to maintain their self-renewal and identities.

Keywords Polycomb repressive complexes      gene silencing      CpG islands      stem cells      self-renewal     
Corresponding Authors: Jin He   
Just Accepted Date: 25 April 2016   Online First Date: 05 May 2016    Issue Date: 17 May 2016
 Cite this article:   
Jin He. Function of Polycomb repressive complexes in stem cells[J]. Front. Biol., 2016, 11(2): 65-74.
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Fig.1  Polycomb repressive complexes in mammals. A. The core components of PRC1 include RING1A/1B and Polycomb group ring finger proteins (PCGFs). PRC1 is sub-divided into six groups (PRC1.1-1.6) based on different PCGF proteins associated with the core components. The canonical PRC1 (cPRC1) and non-canonical PRC1 (ncPRC1) sub-groups have CBX and RYBP/YAF2 proteins associated with the core component respectively. The histone lysine demethylase 2B (KDM2B) in the PRC1.1 binds to CpG islands through its CxxC-ZF domain. B. The core components of PRC2 are composed of enhancer of zester homolog 2 (EZH2) or EZH1, embryonic ectoderm development (EED), and suppressor or zeste 12 (SUZ12). The PRC2 core components interact with different binding partners, such as JARID2, AEBP2, and PCL proteins, to form various PRC2 sub-complexes.
Fig.2  Polycomb repressive complexes in mammals. (A) The core components of PRC1 include RING1A/1B and Polycomb group ring finger proteins (PCGFs). PRC1 is sub-divided into six groups (PRC1.1-1.6) based on different PCGF proteins associated with the core components. The canonical PRC1 (cPRC1) and non-canonical PRC1 (ncPRC1) sub-groups have CBX and RYBP/YAF2 proteins associated with the core components respectively. The histone lysine demethylase 2B (KDM2B) in the PRC1.1 binds to CpG islands through its CxxC-ZF domain. (B) The core components of PRC2 are composed of enhancer of zester homolog 2 (EZH2) or EZH1, embryonic ectoderm development (EED), and suppressor of zeste 12 (SUZ12). The PRC2 core components interact with different binding partners, such as JARID2, AEBP2, and PCL proteins, to form various PRC2 sub-complexes.
Fig.3  Functions of Polycomb repressive complexes in stem cell maintenance and lineage differentiation. PRCs are recruited to the CGI promoters of INK4A/ARF/INK4B locus and key developmental genes in stem cells, and maintain the gene silencing by blocking non-specific transcriptional signals from environments. Silencing of both INK4A/ARF/INK4B locus and differentiation genes is essential for the maintenance of stem cell self-renewal. During lineage differentiation, strong lineage-specific transcriptional signals remove PRCs from promoters and drive the expression of lineage-specific genes.
1 Abraham B J, Cui K, Tang Q, Zhao K (2013). Dynamic regulation of epigenomic landscapes during hematopoiesis. BMC Genomics, 14(1): 193
doi: 10.1186/1471-2164-14-193
2 Ballare C, Lange M, Lapinaite A, Martin G M, Morey L, Pascual G, Liefke R, Simon B, Shi Y, Gozani O, Carlomagno T, Benitah S A, Di Croce L (2012). Phf19 links methylated Lys36 of histone H3 to regulation of Polycomb activity. Nat Struct Mol Biol, 19(12): 1257–1265
doi: 10.1038/nsmb.2434
3 Bernstein B E, Mikkelsen T S, Xie X, Kamal M, Huebert D J, Cuff J, Fry B, Meissner A, Wernig M, Plath K, Jaenisch R, Wagschal A, Feil R, Schreiber S L, Lander E S (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
4 Blackledge N P, Farcas A M, Kondo T, King H W, McGouran J F, Hanssen L L, Ito S, Cooper S, Kondo K, Koseki Y, Ishikura T, Long H K, Sheahan T W, Brockdorff N, Kessler B M, Koseki H, Klose R J (2014). Variant PRC1 complex-dependent H2A ubiquitylation drives PRC2 recruitment and polycomb domain formation. Cell, 157(6): 1445–1459
doi: 10.1016/j.cell.2014.05.004
5 Cai L, Rothbart S B, Lu R, Xu B, Chen W Y, Tripathy A, Rockowitz S, Zheng D, Patel D J, Allis C D, Strahl B D, Song J, Wang G G (2013). An H3K36 methylation-engaging Tudor motif of polycomb-like proteins mediates PRC2 complex targeting. Mol Cell, 49(3): 571–582
doi: 10.1016/j.molcel.2012.11.026
6 Cao R, Wang L, Wang H, Xia L, Erdjument-Bromage H, Tempst P, Jones R S, Zhang Y (2002). Role of histone H3 lysine 27 methylation in Polycomb-group silencing. Science, 298(5595): 1039–1043
doi: 10.1126/science.1076997
7 Chan C S, Rastelli L, Pirrotta V (1994). A Polycomb response element in the Ubx gene that determines an epigenetically inherited state of repression. EMBO J, 13: 2553–2564
8 Cui K, Zang C, Roh T Y, Schones D E, Childs R W, Peng W, Zhao K (2009). Chromatin signatures inmultipotent humanhematopoietic stem cells indicatethefate of bivalent genes during differentiation. Cell Stem Cell, 4(1): 80–93
doi: 10.1016/j.stem.2008.11.011
9 Czermin B, Melfi R, McCabe D, Seitz V, Imhof A, Pirrotta V (2002). Drosophila enhancer of Zeste/ESC complexes have a histone H3 methyltransferase activity that marks chromosomal Polycomb sites. Cell, 111(2): 185–196
doi: 10.1016/S0092-8674(02)00975-3
10 de Napoles M, Mermoud J E, Wakao R, Tang Y A, Endoh M, Appanah R, Nesterova T B, Silva J, Otte A P, Vidal M, Koseki H, Brockdorff N (2004). Polycomb group proteins Ring1A/B link ubiquitylation of histone H2A to heritable gene silencing and X inactivation. Dev Cell, 7(5): 663–676
doi: 10.1016/j.devcel.2004.10.005
11 Deaton A M, Bird A (2011). CpG islands and the regulation of transcription. Genes Dev, 25(10): 1010–1022
doi: 10.1101/gad.2037511
12 Dietrich N, Lerdrup M, Landt E, Agrawal-Singh S, Bak M, Tommerup N, Rappsilber J, Sodersten E, Hansen K (2012). REST-mediated recruitment of polycomb repressor complexes in mammalian cells. PLoS Genet, 8(3): e1002494
doi: 10.1371/journal.pgen.1002494
13 Endoh M, Endo T A, Endoh T, Isono K, Sharif J, Ohara O, Toyoda T, Ito T, Eskeland R, Bickmore W A, Vidal M, Bernstein B E, Koseki H (2012). Histone H2A mono-ubiquitination is a crucial step to mediate PRC1-dependent repression of developmental genes to maintain ES cell identity. PLoS Genet, 8(7): e1002774
doi: 10.1371/journal.pgen.1002774
14 Eskeland R, Freyer E, Leeb M, Wutz A, Bickmore W A (2010a). Histone acetylation and the maintenance of chromatin compaction by Polycomb repressive complexes. Cold Spring Harb Symp Quant Biol, 75(0): 71–78
doi: 10.1101/sqb.2010.75.053
15 Eskeland R, Leeb M, Grimes G R, Kress C, Boyle S, Sproul D, Gilbert N, Fan Y, Skoultchi A I, Wutz A, Bickmore W A (2010b). Ring1B compacts chromatin structure and represses gene expression independent of histone ubiquitination. Mol Cell, 38(3): 452–464
doi: 10.1016/j.molcel.2010.02.032
16 Evans M J, Kaufman M H (1981). Establishment in culture of pluripotential cells from mouse embryos. Nature, 292(5819): 154–156
doi: 10.1038/292154a0
17 Farcas A M, Blackledge N P, Sudbery I, Long H K, McGouran J F, Rose N R, Lee S, Sims D, Cerase A, Sheahan T W, Koseki H, Brockdorff N, Ponting C P, Kessler B M, Klose R J (2012). KDM2B links the Polycomb Repressive Complex 1 (PRC1) to recognition of CpG islands. eLife, 1: e00205
doi: 10.7554/eLife.00205
18 Fischle W, Wang Y, Jacobs S A, Kim Y, Allis C D, Khorasanizadeh S (2003). Molecular basis for the discrimination of repressive methyl-lysine marks in histone H3 by Polycomb and HP1 chromodomains. Genes Dev, 17(15): 1870–1881
doi: 10.1101/gad.1110503
19 Gao Z, Lee P, Stafford J M, von Schimmelmann M, Schaefer A, Reinberg D (2014). An AUTS2-Polycomb complex activates gene expression in the CNS. Nature, 516(7531): 349–354
doi: 10.1038/nature13921
20 Gao Z, Zhang J, Bonasio R, Strino F, Sawai A, Parisi F, Kluger Y, Reinberg D (2012). PCGF homologs, CBX proteins, and RYBP define functionally distinct PRC1 family complexes. Mol Cell, 45(3): 344–356
doi: 10.1016/j.molcel.2012.01.002
21 Gaytan de Ayala Alonso A, Gutierrez L, Fritsch C, Papp B, Beuchle D, Muller J (2007). A genetic screen identifies novel polycomb group genes in <?Pub Caret?>Drosophila. Genetics, 176(4): 2099–2108
doi: 10.1534/genetics.107.075739
22 Grau D J, Antao J M, Kingston R E (2010). Functional dissection of Polycomb repressive complex 1 reveals the importance of a charged domain. Cold Spring Harb Symp Quant Biol, 75(0): 61–70
doi: 10.1101/sqb.2010.75.056
23 He J, Kallin E M, Tsukada Y, Zhang Y (2008). The H3K36 demethylase Jhdm1b/Kdm2b regulates cell proliferation and senescence through p15(Ink4b). Nat Struct Mol Biol, 15(11): 1169–1175
doi: 10.1038/nsmb.1499
24 He J, Nguyen A T, Zhang Y (2011). KDM2b/JHDM1b, an H3K36me2-specific demethylase, is required for initiation and maintenance of acute myeloid leukemia. Blood, 117(14): 3869–3880
doi: 10.1182/blood-2010-10-312736
25 He J, Shen L, Wan M, Taranova O, Wu H, Zhang Y (2013). Kdm2b maintains murine embryonic stem cell status by recruiting PRC1 complex to CpG islands of developmental genes. Nat Cell Biol, 15(4): 373–384
doi: 10.1038/ncb2702
26 Hidalgo I, Herrera-Merchan A, Ligos J M, Carramolino L, Nunez J, Martinez F, Dominguez O, Torres M, Gonzalez S (2012). Ezh1 is required for hematopoietic stem cell maintenance and prevents senescence-like cell cycle arrest. Cell Stem Cell, 11(5): 649–662
doi: 10.1016/j.stem.2012.08.001
27 Jiao L, Liu X (2015). Structural basis of histone H3K27 trimethylation by an active polycomb repressive complex 2. Science, 350(6258): aac4383
doi: 10.1126/science.aac4383
28 Kim H, Kang K, Kim J (2009). AEBP2 as a potential targeting protein for Polycomb Repression Complex PRC2. Nucleic Acids Res, 37(9): 2940–2950
doi: 10.1093/nar/gkp149
29 Kim W Y, Sharpless N E (2006). The regulation of INK4/ARF in cancer and aging. Cell, 127(2): 265–275
doi: 10.1016/j.cell.2006.10.003
30 Klauke K, Radulovic V, Broekhuis M, Weersing E, Zwart E, Olthof S, Ritsema M, Bruggeman S, Wu X, Helin K, Bystrykh L, de Haan G (2013). Polycomb Cbx family members mediate the balance between haematopoietic stem cell self-renewal and differentiation. Nat Cell Biol, 15(4): 353–362
doi: 10.1038/ncb2701
31 Kreso A, Dick J E (2014). Evolution of the cancer stem cell model. Cell Stem Cell, 14(3): 275–291
doi: 10.1016/j.stem.2014.02.006
32 Ku M, Koche R P, Rheinbay E, Mendenhall E M, Endoh M, Mikkelsen T S, Presser A, Nusbaum C, Xie X, Chi A S, Adli M, Kasif S, Ptaszek L M, Cowan C A, Lander E S, Koseki H, Bernstein B E (2008). Genomewide analysis of PRC1 and PRC2 occupancy identifies two classes of bivalent domains. PLoS Genet, 4(10): e1000242
doi: 10.1371/journal.pgen.1000242
33 Kuzmichev A, Nishioka K, Erdjument-Bromage H, Tempst P, Reinberg D (2002). Histone methyltransferase activity associated with a human multiprotein complex containing the Enhancer of Zeste protein. Genes Dev, 16(22): 2893–2905
doi: 10.1101/gad.1035902
34 Lessard J, Sauvageau G (2003). Bmi-1 determines the proliferative capacity of normal and leukaemic stem cells. Nature, 423(6937): 255–260
doi: 10.1038/nature01572
35 Lewis E B (1978). A gene complex controlling segmentation in Drosophila. Nature, 276(5688): 565–570
doi: 10.1038/276565a0
36 Li G, Margueron R, Ku M, Chambon P, Bernstein B E, Reinberg D (2010). Jarid2 and PRC2, partners in regulating gene expression. Genes Dev, 24(4): 368–380
doi: 10.1101/gad.1886410
37 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
38 Long H K, Blackledge N P, Klose R J (2013). ZF-CxxC domain-containing proteins, CpG islands and the chromatin connection. Biochem Soc Trans, 41(3): 727–740
doi: 10.1042/BST20130028
39 Luis N M, Morey L, Di Croce L, Benitah S A (2012). Polycomb in stem cells: PRC1 branches out. Cell Stem Cell, 11(1): 16–21
doi: 10.1016/j.stem.2012.06.005
40 Martin G R (1981). Isolation of a pluripotent cell line from early mouse embryos cultured in medium conditioned by teratocarcinoma stem cells. Proc Natl Acad Sci USA, 78(12): 7634–7638
doi: 10.1073/pnas.78.12.7634
41 Mendenhall E M, Koche R P, Truong T, Zhou V W, Issac B, Chi A S, Ku M, Bernstein B E (2010). GC-rich sequence elements recruit PRC2 in mammalian ES cells. PLoS Genet, 6(12): e1001244
doi: 10.1371/journal.pgen.1001244
42 Mikkelsen T S, Ku M, Jaffe D B, Issac B, Lieberman E, Giannoukos G, Alvarez P, Brockman W, Kim T K, Koche R P, Lee W, Mendenhall E, O’Donovan A, Presser A, Russ C, Xie X, Meissner A, Wernig M, Jaenisch R, Nusbaum C, Lander E S, Bernstein B E (2007). Genome-wide maps of chromatin state in pluripotent and lineage-committed cells. Nature, 448(7153): 553–560
doi: 10.1038/nature06008
43 Min J, Zhang Y, Xu R M (2003). Structural basis for specific binding of Polycomb chromodomain to histone H3 methylated at Lys 27. Genes Dev, 17(15): 1823–1828
doi: 10.1101/gad.269603
44 Mochizuki-Kashio M, Mishima Y, Miyagi S, Negishi M, Saraya A, Konuma T, Shinga J, Koseki H, Iwama A (2011). Dependency on the polycomb gene Ezh2 distinguishes fetal from adult hematopoietic stem cells. Blood, 118(25): 6553–6561
doi: 10.1182/blood-2011-03-340554
45 Mohd-Sarip A, Cleard F, Mishra R K, Karch F, Verrijzer C P (2005). Synergistic recognition of an epigenetic DNA element by Pleiohomeotic and a Polycomb core complex. Genes Dev, 19(15): 1755–1760
doi: 10.1101/gad.347005
46 Mohd-Sarip A, Venturini F, Chalkley G E, Verrijzer C P (2002). Pleiohomeotic can link polycomb to DNA and mediate transcriptional repression. Mol Cell Biol, 22(21): 7473–7483
doi: 10.1128/MCB.22.21.7473-7483.2002
47 Molofsky A V, He S, Bydon M, Morrison S J, Pardal R (2005). 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(12): 1432–1437
doi: 10.1101/gad.1299505
48 Molofsky A V, Pardal R, Iwashita T, Park I K, Clarke M F, Morrison S J (2003). Bmi-1 dependence distinguishes neural stem cell self-renewal from progenitor proliferation. Nature, 425(6961): 962–967
doi: 10.1038/nature02060
49 Muller J, Hart C M, Francis N J, Vargas M L, Sengupta A, Wild B, Miller E L, O'Connor M B, Kingston R E, Simon J A (2002). Histone methyltransferase activity of a Drosophila Polycomb group repressor complex. Cell, 111(2): 197–208
doi: 10.1016/S0092-8674(02)00976-5
50 Nusslein-Volhard C, Kluding H, Jurgens G (1985). Genes affecting the segmental subdivision of the Drosophila embryo. Cold Spring Harb Symp Quant Biol, 50(0): 145–154
doi: 10.1101/SQB.1985.050.01.020
51 Onder T T, Kara N, Cherry A, Sinha A U, Zhu N, Bernt K M, Cahan P, Marcarci B O, Unternaehrer J, Gupta P B, Lander E S, Armstrong S A, Daley G Q (2012). Chromatin-modifying enzymes as modulators of reprogramming. Nature, 483(7391): 598–602
doi: 10.1038/nature10953
52 Park I K, Qian D, Kiel M, Becker M W, Pihalja M, Weissman I L, Morrison S J, Clarke M F (2003). Bmi-1 is required for maintenance of adult self-renewing haematopoietic stem cells. Nature, 423(6937): 302–305
doi: 10.1038/nature01587
53 Pasini D, Bracken A P, Hansen J B, Capillo M, Helin K (2007). The polycomb group protein Suz12 is required for embryonic stemcell differentiation. Mol Cell Biol, 27(10): 3769–3779
doi: 10.1128/MCB.01432-06
54 Pasini D, Cloos P A, Walfridsson J, Olsson L, Bukowski J P, Johansen J V, Bak M, Tommerup N, Rappsilber J, Helin K (2010). JARID2 regulates binding of the Polycomb repressive complex 2 to target genes in ES cells. Nature, 464(7286): 306–310
doi: 10.1038/nature08788
55 Pereira J D, Sansom S N, Smith J, Dobenecker M W, Tarakhovsky A, Livesey F J (2010). Ezh2, the histone methyltransferase of PRC2, regulates the balance between self-renewal and differentiation in the cerebral cortex. Proc Natl Acad Sci USA, 107(36): 15957–15962
doi: 10.1073/pnas.1002530107
56 Pfau R, Tzatsos A, Kampranis S C, Serebrennikova O B, Bear S E, Tsichlis P N (2008). Members of a family of JmjC domain-containing oncoproteins immortalize embryonic fibroblasts via aJmjC domain-dependent process. Proc Natl Acad Sci USA, 105(6): 1907–1912
doi: 10.1073/pnas.0711865105
57 Poux S, Melfi R, Pirrotta V (2001). Establishment of Polycomb silencing requires a transient interaction between PC and ESC. Genes Dev, 15(19): 2509–2514
doi: 10.1101/gad.208901
58 Ren X, Kerppola T K (2011). REST interacts with Cbx proteins and regulates polycomb repressive complex 1 occupancy at RE1 elements. Mol Cell Biol, 31(10): 2100–2110
doi: 10.1128/MCB.05088-11
59 Riising E M, Comet I, Leblanc B, Wu X, Johansen J V, 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
60 Rinn J L, Kertesz M, Wang J K, Squazzo S L, Xu X, Brugmann S A, Goodnough L H, Helms J A, Farnham P J, Segal E, Chang H Y (2007). Functional demarcation of active and silent chromatin domains in human HOX loci by noncoding RNAs. Cell, 129(7): 1311–1323
doi: 10.1016/j.cell.2007.05.022
61 Roman-Trufero M, Mendez-Gomez H R, Perez C, Hijikata A, Fujimura Y, Endo T, Koseki H, Vicario-Abejon C, Vidal M (2009). Maintenance of undifferentiated state and self-renewal of embryonic neural stem cells by Polycomb protein Ring1B. Stem Cells, 27(7): 15591570
doi: 10.1002/stem.82
62 Tavares L, Dimitrova E, Oxley D, Webster J, Poot R, Demmers J, Bezstarosti K, Taylor S, Ura H, Koide H, Wutz A, Vidal M, Elderkin S, Brockdorff N (2012). RYBP-PRC1 complexes mediate H2A ubiquitylation at polycomb target sites independently of PRC2 and H3K27me3. Cell, 148(4): 664–678
doi: 10.1016/j.cell.2011.12.029
63 Thornton S R, Butty V L, Levine S S, Boyer L A (2014). Polycomb Repressive Complex 2 regulates lineage fidelity during embryonic stem cell differentiation. PLoS ONE, 9(10): e110498
doi: 10.1371/journal.pone.0110498
64 Ueda K, Yoshimi A, Kagoya Y, Nishikawa S, Marquez V E, Nakagawa M, Kurokawa M (2014). Inhibition of histone methyltransferase EZH2 depletes leukemia stem cell of mixed lineage leukemia fusion leukemia through upregulation of p16. Cancer Sci, 105: 512–519
65 Utikal J, Polo J M, Stadtfeld M, Maherali N, Kulalert W, Walsh R M, Khalil A, Rheinwald J G, Hochedlinger K (2009). Immortalization eliminates a roadblock during cellular reprogramming into iPS cells. Nature, 460(7259): 1145–1148
doi: 10.1038/nature08285
66 van den Boom V, Rozenveld-Geugien M, Bonardi F, Malanga D, van Gosliga D, Heijink A M, Viglietto G, Morrone G, Fusetti F, Vellenga E, Schuringa J J (2013). Nonredundant and locus-specific gene repression functions of PRC1 paralog family members in human hematopoietic stem/progenitor cells. Blood, 121(13): 2452–2461
doi: 10.1182/blood-2012-08-451666
67 van der Stoop P, Boutsma E A, Hulsman D, Noback S, Heimerikx M, Kerkhoven R M, Voncken J W, Wessels L F, van Lohuizen M (2008). Ubiquitin E3 ligase Ring1b/Rnf2 of polycomb repressive complex 1 contributes to stable maintenance of mouse embryonic stem cells. PLoS ONE, 3(5): e2235
doi: 10.1371/journal.pone.0002235
68 Walker E, Chang W Y, Hunkapiller J, Cagney G, Garcha K, Torchia J, Krogan N J, Reiter J F, Stanford W L (2010). Polycomb-like 2 associates with PRC2 and regulates transcriptional networks during mouse embryonic stem cell self-renewal and differentiation. Cell Stem Cell, 6(2): 153–166
doi: 10.1016/j.stem.2009.12.014
69 Wang H, Wang L, Erdjument-Bromage H, Vidal M, Tempst P, Jones R S, Zhang Y (2004a). Role of histone H2A ubiquitination in Polycomb silencing. Nature, 431(7010): 873–878
doi: 10.1038/nature02985
70 Wang L, Brown J L, Cao R, Zhang Y, Kassis J A, Jones R S (2004b). Hierarchical recruitment of polycomb group silencing complexes. Mol Cell, 14(5): 637–646
doi: 10.1016/j.molcel.2004.05.009
71 Woo C J, Kharchenko P V, Daheron L, Park P J, Kingston R E (2010). A region of the human HOXD cluster that confers polycomb-group responsiveness. Cell, 140(1): 99–110
doi: 10.1016/j.cell.2009.12.022
72 Wu X, Johansen J V, Helin K (2013). Fbxl10/Kdm2b recruits polycomb repressive complex 1 to CpG islands and regulates H2A ubiquitylation. Mol Cell, 49(6): 1134–1146
doi: 10.1016/j.molcel.2013.01.016
73 Xie H, Xu J, Hsu J H, Nguyen M, Fujiwara Y, Peng C, Orkin S H (2014). Polycomb repressive complex 2 regulates normal hematopoietic stem cell function in a developmental-stage-specific manner. Cell Stem Cell, 14(1): 68–80
doi: 10.1016/j.stem.2013.10.001
74 Xu B, On D M, Ma A, Parton T, Konze K D, Pattenden S G, Allison D F, Cai L, Rockowitz S, Liu S, Liu Y, Li F, Vedadi M, Frye S V, Garcia B A, Zheng D, Jin J, Wang G G (2015). Selective inhibition of EZH2 and EZH1 enzymatic activity by a small molecule suppresses MLL-rearranged leukemia. Blood, 125(2): 346–357
doi: 10.1182/blood-2014-06-581082
75 Xu K, Wu Z J, Groner A C, He H H, Cai C, Lis R T, Wu X, Stack E C, Loda M, Liu T, Xu H, Cato L, Thornton J E, Gregory R I, Morrissey C, Vessella R L, Montironi R, Magi-Galluzzi C, Kantoff P W, Balk S P, Liu X S, Brown M (2012). EZH2 oncogenic activity in castration-resistant prostate cancer cells is Polycomb-independent. Science, 338(6113): 1465–1469
doi: 10.1126/science.1227604
76 Ying Q L, 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
77 Yu M, Mazor T, Huang H, Huang H T, Kathrein K L, Woo A J, Chouinard C R, Labadorf A, Akie T E, Moran T B, Xie H, Zacharek S, Taniuchi I, Roeder R G, Kim C F, Zon L I, Fraenkel E, Cantor A B (2012). Direct recruitment of polycomb repressive complex 1 to chromatin by core binding transcription factors. Mol Cell, 45(3): 330–343
doi: 10.1016/j.molcel.2011.11.032
78 Yuan J, Takeuchi M, Negishi M, Oguro H, Ichikawa H, Iwama A (2011). Bmi1 is essential for leukemic reprogramming of myeloid progenitor cells. Leukemia, 25(8): 1335–1343
doi: 10.1038/leu.2011.85
79 Zhang Z, Jones A, Sun C W, Li C, Chang C W, Joo H Y, Dai Q, Mysliwiec M R, Wu L C, Guo Y, Yang W, Liu K, Pawlik K M, Erdjument-Bromage H, Tempst P, Lee Y, Min J, Townes T M, Wang H (2011). PRC2 complexes with JARID2, MTF2, and esPRC2p48 in ES cells to modulate ES cell pluripotency and somatic cell reprogramming. Stem Cells, 29(2): 229–240
doi: 10.1002/stem.578
80 Zhao J, Sun B K, Erwin J A, Song J J, Lee J T (2008). Polycomb proteins targeted by a short repeat RNA to the mouse X chromosome. Science, 322(5902): 750–756
doi: 10.1126/science.1163045
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[4] Paul J. Lucassen,Charlotte A. Oomen. Stress, hippocampal neurogenesis and cognition: functional correlations[J]. Front. Biol., 2016, 11(3): 182-192.
[5] Fatih Semerci,Mirjana Maletic-Savatic. Transgenic mouse models for studying adult neurogenesis[J]. Front. Biol., 2016, 11(3): 151-167.
[6] Stuart J. Grice,Ji-Long Liu. A SteMNess perspective of survival motor neuron function: splicing factors in stem cell biology and disease[J]. Front. Biol., 2015, 10(4): 297-309.
[7] Massimo Bonora,Paolo Pinton,Keisuke Ito. Mitochondrial control of hematopoietic stem cell balance and hematopoiesis[J]. Front. Biol., 2015, 10(2): 117-124.
[8] Gary R. HIME,Nicole SIDDALL,Katja HORVAY,Helen E. ABUD. Analyzing stem cell dynamics: use of cutting edge genetic approaches in model organisms[J]. Front. Biol., 2015, 10(1): 1-10.
[9] Brandoch D. COOK. Modeling murine yolk sac hematopoiesis with embryonic stem cell culture systems[J]. Front. Biol., 2014, 9(5): 339-346.
[10] Wei Bin FANG,Min YAO,Nikki CHENG. Priming cancer cells for drug resistance: role of the fibroblast niche[J]. Front. Biol., 2014, 9(2): 114-126.
[11] Adalto PONTES, Yonggang ZHANG, Wenhui HU. Novel functions of GABA signaling in adult neurogenesis[J]. Front Biol, 2013, 8(5): 496-507.
[12] Bipasha MUKHERJEE-CLAVIN, Mark TOMISHIMA, Gabsang LEE. Current approaches for efficient genetic editing in human pluripotent stem cells[J]. Front Biol, 2013, 8(5): 461-467.
[13] Iouri CHEPELEV, Xin CHEN. Alternative splicing switching in stem cell lineages[J]. Front Biol, 2013, 8(1): 50-59.
[14] Yonggang ZHANG, Wenhui HU. NFκB signaling regulates embryonic and adult neurogenesis[J]. Front Biol, 2012, 7(4): 277-291.
[15] Ulrike SCHUMANN, Mick AYLIFFE, Kemal KAZAN, Ming-Bo WANG. RNA silencing in fungi[J]. Front Biol, 2010, 5(6): 478-494.
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