A direct physical interaction between Nanog and Sox2 regulates embryonic stem cell self-renewal

EMBO Journal

Volumn 32, Issue 16, 2013, Pages 2231-2247

  Gagliardi, Alessia ^a   Mullin, Nicholas P ^a   Ying Tan, Zi ^a,d   Colby, Douglas ^a   Kousa, Anastasia I ^a   Halbritter, Florian ^a   Weiss, Jason T ^a,e   Felker, Anastasia ^a,f   Bezstarosti, Karel ^b   Favaro, Rebecca ^c   Demmers, Jeroen ^b   Nicolis, Silvia K ^c   Tomlinson, Simon R ^a   Poot, Raymond A ^b   Chambers, Ian ^a  

^a UNIVERSITY OF EDINBURGH   (United Kingdom)

^b ERASMUS MEDICAL CENTER   (Netherlands)

^c UNIVERSITY OF MILANO BICOCCA   (Italy)

^d GENOME INSTITUTE OF SINGAPORE   (Singapore)

^e UNIVERSITY OF EDINBURGH   (United Kingdom)

^f UNIVERSITY OF ZURICH   (Switzerland)

Author keywords

DNA independent interaction; Hydrophobic stacking; Pluripotency; Protein interactome; SELEX

Indexed keywords

ALANINE; PHENYLALANINE; TRANSCRIPTION FACTOR; TRANSCRIPTION FACTOR NANOG; TRANSCRIPTION FACTOR SOX2; TRYPTOPHAN;

ANIMAL CELL; ARTICLE; CELL DIFFERENTIATION; CELL RENEWAL; CHROMATIN; CONTROLLED STUDY; EMBRYONIC STEM CELL; IMMUNOBLOTTING; MUTATION; NONHUMAN; POLYMERASE CHAIN REACTION; PRIORITY JOURNAL; PROTEIN PHOSPHORYLATION; PROTEIN PROTEIN INTERACTION; RNA PROCESSING; UBIQUITINATION;

ANIMALS; CELL PROLIFERATION; COLONY-FORMING UNITS ASSAY; EMBRYONIC STEM CELLS; HOMEODOMAIN PROTEINS; IMMUNOBLOTTING; IMMUNOPRECIPITATION; MICE; PLASMIDS; PROTEIN INTERACTION DOMAINS AND MOTIFS; PROTEIN INTERACTION MAPPING; SELEX APTAMER TECHNIQUE; SOXB1 TRANSCRIPTION FACTORS; TRYPTOPHAN; TYROSINE;

EID: 84882449803     PISSN: 02614189     EISSN: 14602075     Source Type: Journal    
DOI: 10.1038/emboj.2013.161     Document Type: Article

References (67)

1. Ambrosetti DC, Basilico C, Dailey L (1997) Synergistic activation of the fibroblast growth factor 4 enhancer by Sox2 and Oct-3 depends on protein-protein interactions facilitated by a specific spatial arrangement of factor binding sites. Mol Cell Biol 17: 6321-6329
2. Ambrosetti DC, Scholer HR, Dailey L, Basilico C (2000) Modulation of the activity of multiple transcriptional activation domains by the DNA binding domains mediates the synergistic action of Sox2 and Oct-3 on the fibroblast growth factor-4 enhancer. J Biol Chem 275: 23387-23397
3. Avilion AA, Nicolis SK, Pevny LH, Perez L, Vivian N, Lovell-Badge R (2003) Multipotent cell lineages in early mouse development depend on SOX2 function. Genes Dev 17: 126-140
4. Bailey TL, Boden M, Buske FA, Frith M, Grant CE, Clementi L, Ren J, Li WW, Noble WS (2009) MEME SUITE: tools for motif discovery and searching. Nucleic Acids Res 37(Web Server issue): W202-W208
5. Bogan AA, Thorn KS (1998) Anatomy of hot spots in protein interfaces. J Mol Biol 280: 1-9
6. Brookes E, de Santiago I, Hebenstreit D, Morris KJ, Carroll T, Xie SQ, Stock JK, Heidemann M, Eick D, Nozaki N, Kimura H, Ragoussis J, Teichmann SA, Pombo A (2012) Polycomb associates genome-wide with a specific RNA polymerase II variant, and regulates metabolic genes in ESCs. Cell Stem Cell 10: 157-170
7. Chambers I, Colby D, Robertson M, Nichols J, Lee S, Tweedie S, Smith A (2003) Functional expression cloning of Nanog, a pluripotency sustaining factor in embryonic stem cells. Cell 113: 643-655
8. Chambers I, Silva J, Colby D, Nichols J, Nijmeijer B, Robertson M, Vrana J, Jones K, Grotewold L, Smith A (2007) Nanog safeguards pluripotency and mediates germline development. Nature 450: 1230-1234
9. Chen X, Fang F, Liou YC, Ng HH (2008a) Zfp143 regulates Nanog through modulation of Oct4 binding. Stem Cells 26: 2759-2767
10. Chen X, Xu H, Yuan P, Fang F, Huss M, Vega VB, Wong E, Orlov YL, Zhang W, Jiang J, Loh YH, Yeo HC, Yeo ZX, Narang V, Govindarajan KR, Leong B, Shahab A, Ruan Y, Bourque G, Sung WK et al (2008b) Integration of external signaling pathways with the core transcriptional network in embryonic stem cells. Cell 133: 1106-1117
11. Costa Y, Ding J, Theunissen TW, Faiola F, Hore TA, Shliaha PV, Fidalgo M, Saunders A, Lawrence M, Dietmann S, Das S, Levasseur DN, Li Z, Xu M, Reik W, Silva JC, Wang J (2013) NANOG-dependent function of TET1 and TET2 in establishment of pluripotency. Nature 495: 370-374
12. DeLano WL (2002) Unraveling hot spots in binding interfaces: progress and challenges. Curr Opin Struct Biol 12: 14-20
13. Dignam JD, Lebovitz RM, Roeder RG (1983) Accurate transcription initiation by RNA polymerase II in a soluble extract from isolated mammalian nuclei. Nucleic Acids Res 11: 1475-1489
14. Ding J, Xu H, Faiola F, Ma'ayan A, Wang J (2012) Oct4 links multiple epigenetic pathways to the pluripotency network. Cell Res 22: 155-167
15. Engelen E, Akinci U, Bryne JC, Hou J, Gontan C, Moen M, Szumska D, Kockx C, van Ijcken W, Dekkers DH, Demmers J, Rijkers EJ, Bhattacharya S, Philipsen S, Pevny LH, Grosveld FG, Rottier RJ, Lenhard B, Poot RA (2011) Sox2 cooperates with Chd7 to regulate genes that are mutated in human syndromes. Nat Genet 43: 607-611
16. Favaro R, Valotta M, Ferri AL, Latorre E, Mariani J, Giachino C, Lancini C, Tosetti V, Ottolenghi S, Taylor V, Nicolis SK (2009) Hippocampal development and neural stem cell maintenance require Sox2-dependent regulation of Shh. Nat Neurosci 12: 1248-1256
17. Festuccia N, Osorno R, Halbritter F, Karwacki-Neisius V, Navarro P, Colby D, Wong F, Yates A, Tomlinson SR, Chambers I (2012) Esrrb is a direct Nanog target gene that can substitute for Nanog function in pluripotent cells. Cell Stem Cell 11: 477-490
18. Fidalgo M, Faiola F, Pereira CF, Ding J, Saunders A, Gingold J, Schaniel C, Lemischka IR, Silva JC, Wang J (2012) Zfp281 mediates Nanog autorepression through recruitment of the NuRD complex and inhibits somatic cell reprogramming. Proc Natl Acad Sci USA 109: 16202-16207
19. Gao Z, Cox JL, Gilmore JM, Ormsbee BD, Mallanna SK, Washburn MP, Rizzino A (2012) Determination of protein interactome of transcription factor Sox2 in embryonic stem cells engineered for inducible expression of four reprogramming factors. J Biol Chem 287: 11384-11397
20. Genzor CG, Perales-Alcon A, Sancho J, Romero A (1996) Closure of a tyrosine/tryptophan aromatic gate leads to a compact fold in apo flavodoxin. Nat Struct Biol 3: 329-332
21. Halbritter F, Vaidya HJ, Tomlinson SR (2012) GeneProf: analysis of high-throughput sequencing experiments. Nat Methods 9: 7-8
22. Han JD, Bertin N, Hao T, Goldberg DS, Berriz GF, Zhang LV, Dupuy D, Walhout AJ, Cusick ME, Roth FP, Vidal M (2004) Evidence for dynamically organized modularity in the yeast protein-protein interaction network. Nature 430: 88-93
23. Harley VR, Lovell-Badge R, Goodfellow PN (1994) Definition of a consensus DNA binding site for SRY. Nucleic Acids Res 22: 1500-1501
24. Hatano SY, Tada M, Kimura H, Yamaguchi S, Kono T, Nakano T, Suemori H, Nakatsuji N, Tada T (2005) Pluripotential competence of cells associated with Nanog activity. Mech Dev 122: 67-79
25. Ho SN, Hunt HD, Horton RM, Pullen JK, Pease LR (1989) Sitedirected mutagenesis by overlap extension using the polymerase chain reaction. Gene 77: 51-59
26. Hooper M, Hardy K, Handyside A, Hunter S, Monk M (1987) HPRTdeficient (Lesch-Nyhan) mouse embryos derived from germline colonization by cultured cells. Nature 326: 292-295
27. Hutchins AP, Choo SH, Mistri TK, Rahmani M, Woon CT, Ng CK, Jauch R, Robson P (2013) Co-motif discovery identifies an Esrrb- Sox2-DNA ternary complex as a mediator of transcriptional differences between mouse embryonic and epiblast stem cells. Stem Cells 31: 269-281
28. Jang H, Kim TW, Yoon S, Choi SY, Kang TW, Kim SY, Kwon YW, Cho EJ, Youn HD (2012) O-GlcNAc regulates pluripotency and reprogramming by directly acting on core components of the pluripotency network. Cell Stem Cell 11: 62-74
29. Jauch R, Ng CK, Saikatendu KS, Stevens RC, Kolatkar PR (2008) Crystal structure and DNA binding of the homeodomain of the stem cell transcription factor Nanog. J Mol Biol 376: 758-770
30. Jepsen K, Rosenfeld MG (2002) Biological roles and mechanistic actions of co-repressor complexes. J Cell Sci 115(Pt 4): 689-698
31. Kim J, Chu J, Shen X, Wang J, Orkin SH (2008) An extended transcriptional network for pluripotency of embryonic stem cells. Cell 132: 1049-1061
32. Laemmli UK (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227: 680-685
33. Lam CS, Mistri TK, Foo YH, Sudhaharan T, Gan HT, Rodda D, Lim LH, Chou C, Robson P, Wohland T, Ahmed S (2012) DNAdependent Oct4-Sox2 interaction and diffusion properties characteristic of the pluripotent cell state revealed by fluorescence spectroscopy. Biochem J 448: 21-33
34. Liang J, Wan M, Zhang Y, Gu P, Xin H, Jung SY, Qin J, Wong J, Cooney AJ, Liu D, Songyang Z (2008) Nanog and Oct4 associate with unique transcriptional repression complexes in embryonic stem cells. Nat Cell Biol 10: 731-739
35. Ma T, Wang Z, Guo Y, Pei D (2009) The C-terminal pentapeptide of Nanog tryptophan repeat domain interacts with Nac1 and regulates stem cell proliferation but not pluripotency. J Biol Chem 284: 16071-16081
36. Marson A, Levine SS, Cole MF, Frampton GM, Brambrink T, Johnstone S, Guenther MG, Johnston WK, Wernig M, Newman J, Calabrese JM, Dennis LM, Volkert TL, Gupta S, Love J, Hannett N, Sharp PA, Bartel DP, Jaenisch R, Young RA (2008) Connecting microRNA genes to the core transcriptional regulatory circuitry of embryonic stem cells. Cell 134: 521-533
37. Maruyama M, Ichisaka T, Nakagawa M, Yamanaka S (2005) Differential roles for Sox15 and Sox2 in transcriptional control in mouse embryonic stem cells. J Biol Chem 280: 24371-24379
38. Masui S, Nakatake Y, Toyooka Y, Shimosato D, Yagi R, Takahashi K, Okochi H, Okuda A, Matoba R, Sharov AA, Ko MS, Niwa H (2007) Pluripotency governed by Sox2 via regulation of Oct3/4 expression in mouse embryonic stem cells. Nat Cell Biol 9: 625-635
39. McDonel P, Costello I, Hendrich B (2009) Keeping things quiet: roles of NuRD and Sin3 co-repressor complexes during mammalian development. Int J Biochem Cell Biol 41: 108-116
40. Mitsui K, Tokuzawa Y, Itoh H, Segawa K, Murakami M, Takahashi K, Maruyama M, Maeda M, Yamanaka S (2003) The homeoprotein Nanog is required for maintenance of pluripotency in mouse epiblast and ES cells. Cell 113: 631-642
41. Moretto-Zita M, Jin H, Shen Z, Zhao T, Briggs SP, Xu Y (2010) Phosphorylation stabilizes Nanog by promoting its interaction with Pin1. Proc Natl Acad Sci USA 107: 13312-13317
42. Mullin NP, Chambers I (2012) The function of Nanog in pluripotency. In Nuclear Reprogramming and Stem Cells, Ainscough J, Yamanaka S, Tada T (eds), pp 99-112. New York: Springer
43. Mullin NP, Yates A, Rowe AJ, Nijmeijer B, Colby D, Barlow PN, Walkinshaw MD, Chambers I (2008) The pluripotency rheostat Nanog functions as a dimer. Biochem J 411: 227-231
44. Navarro P, Festuccia N, Colby D, Gagliardi A, Mullin NP, Zhang W, Karwacki-Neisius V, Osorno R, Kelly D, Robertson M, Chambers I (2012a) OCT4/SOX2-independent Nanog autorepression modulates heterogeneous Nanog gene expression in mouse ES cells. EMBO J 31: 4547-4562
45. Navarro P, Festuccia N, Colby D, Gagliardi A, Mullin NP, Zhang W, Karwacki-Neisius V, Osorno R, Kelly D, Robertson M, Chambers I (2012b) OCT4/SOX2-independent Nanog autorepression modulates heterogeneous Nanog gene expression in mouse ES cells. EMBO J 31: 4547-4562
46. Noble SM, Carnahan VE, Moore LB, Luntz T, Wang H, Ittoop OR, Stimmel JB, Davis-Searles PR, Watkins RE, Wisely GB, LeCluyse E, Tripathy A, McDonnell DP, Redinbo MR (2006) Human PXR forms a tryptophan zipper-mediated homodimer. Biochemistry 45: 8579-8589
47. Pardo M, Lang B, Yu L, Prosser H, Bradley A, Babu MM, Choudhary J (2010) An expanded Oct4 interaction network: implications for stem cell biology, development, and disease. Cell Stem Cell 6: 382-395
48. Parisi S, Cozzuto L, Tarantino C, Passaro F, Ciriello S, Aloia L, Antonini D, De Simone V, Pastore L, Russo T (2010) Direct targets of Klf5 transcription factor contribute to the maintenance of mouse embryonic stem cell undifferentiated state. BMC Biol 8: 128
49. Perkins DN, Pappin DJ, Creasy DM, Cottrell JS (1999) Probabilitybased protein identification by searching sequence databases using mass spectrometry data. Electrophoresis 20: 3551-3567
50. Qin J, Whyte WA, Anderssen E, Apostolou E, Chen HH, Akbarian S, Bronson RT, Hochedlinger K, Ramaswamy S, Young RA, Hock H (2012) The polycomb group protein L3mbtl2 assembles an atypical PRC1-family complex that is essential in pluripotent stem cells and early development. Cell Stem Cell 11: 319-332
51. Remenyi A, Lins K, Nissen LJ, Reinbold R, Scholer HR, Wilmanns M (2003) Crystal structure of a POU/HMG/DNA ternary complex suggests differential assembly of Oct4 and Sox2 on two enhancers. Genes Dev 17: 2048-2059
52. Reynolds N, Latos P, Hynes-Allen A, Loos R, Leaford D, O'Shaughnessy A, Mosaku O, Signolet J, Brennecke P, Kalkan T, Costello I, Humphreys P, MansfieldW, Nakagawa K, Strouboulis J, Behrens A, Bertone P, Hendrich B (2012) NuRD suppresses pluripotency gene expression to promote transcriptional heterogeneity and lineage commitment. Cell Stem Cell 10: 583-594
53. Rogers MS, Tyler EM, Akyumani N, Kurtis CR, Spooner RK, Deacon SE, Tamber S, Firbank SJ, Mahmoud K, Knowles PF, Phillips SE, McPherson MJ, Dooley DM (2007) The stacking tryptophan of galactose oxidase: a second-coordination sphere residue that has profound effects on tyrosyl radical behavior and enzyme catalysis. Biochemistry 46: 4606-4618
54. Rugg-Gunn PJ, Cox BJ, Lanner F, Sharma P, Ignatchenko V, McDonald AC, Garner J, Gramolini AO, Rossant J, Kislinger T (2012) Cell-surface proteomics identifies lineage-specific markers of embryo-derived stem cells. Dev Cell 22: 887-901
55. Shi W, Wang H, Pan G, Geng Y, Guo Y, Pei D (2006) Regulation of the pluripotency marker Rex-1 by Nanog and Sox2. J Biol Chem 281: 23319-23325
56. Singh AM, Hamazaki T, Hankowski KE, Terada N (2007) A heterogeneous expression pattern for Nanog in embryonic stem cells. Stem Cells 25: 2534-2542
57. Smith AG (1991) Culture and differentiation of embryonic stem cells. J Tiss Cult Meth 13: 89-94
58. Surface LE, Thornton SR, Boyer LA (2010) Polycomb group proteins set the stage for early lineage commitment. Cell Stem Cell 7: 288-298
59. Ura H, Murakami K, Akagi T, Kinoshita K, Yamaguchi S, Masui S, Niwa H, Koide H, Yokota T (2011) Eed/Sox2 regulatory loop controls ES cell self-renewal through histone methylation and acetylation. EMBO J 30: 2190-2204
60. van den Berg DL, Snoek T, Mullin NP, Yates A, Bezstarosti K, Demmers J, Chambers I, Poot RA (2010) An Oct4-centered protein interaction network in embryonic stem cells. Cell Stem Cell 6: 369-381
61. Wang J, Rao S, Chu J, Shen X, Levasseur DN, Theunissen TW, Orkin SH (2006) A protein interaction network for pluripotency of embryonic stem cells. Nature 444: 364-368
62. Wang Z, Ma T, Chi X, Pei D (2008) Aromatic residues in the C-terminal domain 2 are required for Nanog to mediate LIFindependent self-renewal of mouse embryonic stem cells. J Biol Chem 283: 4480-4489
63. 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: 307-319
64. Wu Q, Chen X, Zhang J, Loh YH, Low TY, Zhang W, Zhang W, Sze SK, Lim B, Ng HH (2006) Sall4 interacts with Nanog and cooccupies Nanog genomic sites in embryonic stem cells. J Biol Chem 281: 24090-24094
65. Yates A, Chambers I (2005) The homeodomain protein Nanog and pluripotency in mouse embryonic stem cells. Biochem Soc Trans 33(Pt 6): 1518-1521
66. Yuan H, Corbi N, Basilico C, Dailey L (1995) Developmental-specific activity of the FGF-4 enhancer requires the synergistic action of Sox2 and Oct-3. Genes Dev 9: 2635-2645
67. Zappone MV, Galli R, Catena R, Meani N, De Biasi S, Mattei E, Tiveron C, Vescovi AL, Lovell-Badge R, Ottolenghi S, Nicolis SK (2000) Sox2 regulatory sequences direct expression of a (beta)- geo transgene to telencephalic neural stem cells and precursors of the mouse embryo, revealing regionalization of gene expression in CNS stem cells. Development 127: 2367-2382