POU5F1 (OCT4), SOX2, NANOG repress genes related to differentiation (Homo sapiens)

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2, 10, 11, 13, 14, 17...10, 14, 16, 24, 26...1, 4, 10, 14, 15, 18...5, 8, 10, 14, 24...3, 7, 9, 10, 21...10, 25, 26, 286, 10, 23, 24, 26...9, 10, 12, 22, 24...nucleoplasmHHEX gene NANOG POU5F1 POU5F1:NANOG:GATA6geneNANOG POU5F1SOX2POU5F1:SOX2:NANOG:TSC22D1 geneNANOG CDX2 gene TSC22D1 gene POU5F1:SOX2:NANOG:GSC genePOU5F1:SOX2:NANOG:HHEX geneSOX2 NANOGSOX2 NANOG POU5F1:SOX2:NANOG:DKK1 geneDKK1 geneGSC geneSOX2 POU5F1 GATA6 gene DKK1 gene SOX2 POU5F1 POU5F1 HHEX geneSOX2 SOX2 GATA6 geneNANOG NANOG POU5F1 EOMES geneEOMES gene POU5F1:SOX2:NANOG:CDX2 genePOU5F1:SOX2:NANOG:EOMES geneGSC gene NANOG CDX2 genePOU5F1 TSC22D1 genePOU5F1 10, 2810, 2810, 24, 2810, 14, 18, 2810, 2810, 2810, 14, 18, 28


Description

POU5F1 (OCT4), SOX2, and NANOG bind elements in the promoters of target genes. The target genes of each transcription factor overlap extensively: POU5F1, SOX2, and NANOG co-occupy at least 353 genes (Boyer et al. 2005). About half of POU5F1 targets also bind SOX2 and about 90% of these also bind NANOG (Boyer et al. 2005). Upon binding the transcription factors activate expression of one subset of target genes in the core transcriptional network of pluripotent stem cells and repress another subset (Kim et al. 2006, Matoba et al. 2006, Player et al. 2006, Assou et al. 2007, Babaie et al. 2007, Chavez et al. 2009, Jung et al. 2010). The target genes listed in this module are the repressed genes. Caution must be used when making inferences about human stem cells from mouse stem cells because of significant differences between the two species (Ginis et al. 2004). Source:Reactome.

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Bibliography

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  1. Wang Y, Smedberg JL, Cai KQ, Capo-Chichi DC, Xu XX.; ''Ectopic expression of GATA6 bypasses requirement for Grb2 in primitive endoderm formation.''; PubMed Europe PMC Scholia
  2. Rivera-Pérez JA, Mallo M, Gendron-Maguire M, Gridley T, Behringer RR.; ''Goosecoid is not an essential component of the mouse gastrula organizer but is required for craniofacial and rib development.''; PubMed Europe PMC Scholia
  3. Chavez L, Bais AS, Vingron M, Lehrach H, Adjaye J, Herwig R.; ''In silico identification of a core regulatory network of OCT4 in human embryonic stem cells using an integrated approach.''; PubMed Europe PMC Scholia
  4. Yan X, Zhang J, Pan L, Wang P, Xue H, Zhang L, Gao X, Zhao X, Ning Y, Chen YG.; ''TSC-22 promotes transforming growth factor β-mediated cardiac myofibroblast differentiation by antagonizing Smad7 activity.''; PubMed Europe PMC Scholia
  5. Rong L, Liu J, Qi Y, Graham AM, Parmacek MS, Li S.; ''GATA-6 promotes cell survival by up-regulating BMP-2 expression during embryonic stem cell differentiation.''; PubMed Europe PMC Scholia
  6. Teo AK, Arnold SJ, Trotter MW, Brown S, Ang LT, Chng Z, Robertson EJ, Dunn NR, Vallier L.; ''Pluripotency factors regulate definitive endoderm specification through eomesodermin.''; PubMed Europe PMC Scholia
  7. Park SB, Seo KW, So AY, Seo MS, Yu KR, Kang SK, Kang KS.; ''SOX2 has a crucial role in the lineage determination and proliferation of mesenchymal stem cells through Dickkopf-1 and c-MYC.''; PubMed Europe PMC Scholia
  8. Jin VX, O'Geen H, Iyengar S, Green R, Farnham PJ.; ''Identification of an OCT4 and SRY regulatory module using integrated computational and experimental genomics approaches.''; PubMed Europe PMC Scholia
  9. Hunter MP, Wilson CM, Jiang X, Cong R, Vasavada H, Kaestner KH, Bogue CW.; ''The homeobox gene Hhex is essential for proper hepatoblast differentiation and bile duct morphogenesis.''; PubMed Europe PMC Scholia
  10. van den Ameele J, Tiberi L, Bondue A, Paulissen C, Herpoel A, Iacovino M, Kyba M, Blanpain C, Vanderhaeghen P.; ''Eomesodermin induces Mesp1 expression and cardiac differentiation from embryonic stem cells in the absence of Activin.''; PubMed Europe PMC Scholia
  11. Pinzone JJ, Hall BM, Thudi NK, Vonau M, Qiang YW, Rosol TJ, Shaughnessy JD.; ''The role of Dickkopf-1 in bone development, homeostasis, and disease.''; PubMed Europe PMC Scholia
  12. Bernardo AS, Faial T, Gardner L, Niakan KK, Ortmann D, Senner CE, Callery EM, Trotter MW, Hemberger M, Smith JC, Bardwell L, Moffett A, Pedersen RA.; ''BRACHYURY and CDX2 mediate BMP-induced differentiation of human and mouse pluripotent stem cells into embryonic and extraembryonic lineages.''; PubMed Europe PMC Scholia
  13. Yu J, Ershler M, Yu L, Wei M, Hackanson B, Yokohama A, Mitsui T, Liu C, Mao H, Liu S, Liu Z, Trotta R, Liu CG, Liu X, Huang K, Visser J, Marcucci G, Plass C, Belyavsky AV, Caligiuri MA.; ''TSC-22 contributes to hematopoietic precursor cell proliferation and repopulation and is epigenetically silenced in large granular lymphocyte leukemia.''; PubMed Europe PMC Scholia
  14. Kalisz M, Winzi M, Bisgaard HC, Serup P.; ''EVEN-SKIPPED HOMEOBOX 1 controls human ES cell differentiation by directly repressing GOOSECOID expression.''; PubMed Europe PMC Scholia
  15. Player A, Wang Y, Bhattacharya B, Rao M, Puri RK, Kawasaki ES.; ''Comparisons between transcriptional regulation and RNA expression in human embryonic stem cell lines.''; PubMed Europe PMC Scholia
  16. Martinez Barbera JP, Clements M, Thomas P, Rodriguez T, Meloy D, Kioussis D, Beddington RS.; ''The homeobox gene Hex is required in definitive endodermal tissues for normal forebrain, liver and thyroid formation.''; PubMed Europe PMC Scholia
  17. Kong XB, Zhang C.; ''Dickkopf (Dkk) 1 promotes the differentiation of mouse embryonic stem cells toward neuroectoderm.''; PubMed Europe PMC Scholia
  18. Assou S, Le Carrour T, Tondeur S, Ström S, Gabelle A, Marty S, Nadal L, Pantesco V, Réme T, Hugnot JP, Gasca S, Hovatta O, Hamamah S, Klein B, De Vos J.; ''A meta-analysis of human embryonic stem cells transcriptome integrated into a web-based expression atlas.''; PubMed Europe PMC Scholia
  19. Ginis I, Luo Y, Miura T, Thies S, Brandenberger R, Gerecht-Nir S, Amit M, Hoke A, Carpenter MK, Itskovitz-Eldor J, Rao MS.; ''Differences between human and mouse embryonic stem cells.''; PubMed Europe PMC Scholia
  20. 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.; ''Human DNA methylomes at base resolution show widespread epigenomic differences.''; PubMed Europe PMC Scholia
  21. Babaie Y, Herwig R, Greber B, Brink TC, Wruck W, Groth D, Lehrach H, Burdon T, Adjaye J.; ''Analysis of Oct4-dependent transcriptional networks regulating self-renewal and pluripotency in human embryonic stem cells.''; PubMed Europe PMC Scholia
  22. Jung M, Peterson H, Chavez L, Kahlem P, Lehrach H, Vilo J, Adjaye J.; ''A data integration approach to mapping OCT4 gene regulatory networks operative in embryonic stem cells and embryonal carcinoma cells.''; PubMed Europe PMC Scholia
  23. Boyer LA, Lee TI, Cole MF, Johnstone SE, Levine SS, Zucker JP, Guenther MG, Kumar RM, Murray HL, Jenner RG, Gifford DK, Melton DA, Jaenisch R, Young RA.; ''Core transcriptional regulatory circuitry in human embryonic stem cells.''; PubMed Europe PMC Scholia
  24. Choi SJ, Moon JH, Ahn YW, Ahn JH, Kim DU, Han TH.; ''Tsc-22 enhances TGF-beta signaling by associating with Smad4 and induces erythroid cell differentiation.''; PubMed Europe PMC Scholia
  25. Russ AP, Wattler S, Colledge WH, Aparicio SA, Carlton MB, Pearce JJ, Barton SC, Surani MA, Ryan K, Nehls MC, Wilson V, Evans MJ.; ''Eomesodermin is required for mouse trophoblast development and mesoderm formation.''; PubMed Europe PMC Scholia
  26. Kim CG, Lee JJ, Jung DY, Jeon J, Heo HS, Kang HC, Shin JH, Cho YS, Cha KJ, Kim CG, Do BR, Kim KS, Kim HS.; ''Profiling of differentially expressed genes in human stem cells by cDNA microarray.''; PubMed Europe PMC Scholia
  27. Jayaraman PS, Frampton J, Goodwin G.; ''The homeodomain protein PRH influences the differentiation of haematopoietic cells.''; PubMed Europe PMC Scholia
  28. Greber B, Lehrach H, Adjaye J.; ''Silencing of core transcription factors in human EC cells highlights the importance of autocrine FGF signaling for self-renewal.''; PubMed Europe PMC Scholia
  29. Matoba R, Niwa H, Masui S, Ohtsuka S, Carter MG, Sharov AA, Ko MS.; ''Dissecting Oct3/4-regulated gene networks in embryonic stem cells by expression profiling.''; PubMed Europe PMC Scholia
  30. Kunarso G, Chia NY, Jeyakani J, Hwang C, Lu X, Chan YS, Ng HH, Bourque G.; ''Transposable elements have rewired the core regulatory network of human embryonic stem cells.''; PubMed Europe PMC Scholia

History

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CompareRevisionActionTimeUserComment
114881view16:39, 25 January 2021ReactomeTeamReactome version 75
113327view11:39, 2 November 2020ReactomeTeamReactome version 74
112539view15:50, 9 October 2020ReactomeTeamReactome version 73
101452view11:32, 1 November 2018ReactomeTeamreactome version 66
100990view21:10, 31 October 2018ReactomeTeamreactome version 65
100526view19:44, 31 October 2018ReactomeTeamreactome version 64
100073view16:28, 31 October 2018ReactomeTeamreactome version 63
99624view15:01, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
99231view12:44, 31 October 2018ReactomeTeamreactome version 62
93863view13:41, 16 August 2017ReactomeTeamreactome version 61
93428view11:23, 9 August 2017ReactomeTeamreactome version 61
88108view09:57, 26 July 2016RyanmillerOntology Term : 'transcription pathway' added !
88107view09:56, 26 July 2016RyanmillerOntology Term : 'regulatory pathway' added !
86517view09:20, 11 July 2016ReactomeTeamreactome version 56
83186view10:18, 18 November 2015ReactomeTeamVersion54
81557view13:05, 21 August 2015ReactomeTeamNew pathway

External references

DataNodes

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NameTypeDatabase referenceComment
CDX2 gene ProteinENSG00000165556 (ENSEMBL)
CDX2 geneENSG00000165556 (ENSEMBL)
DKK1 gene ProteinENSG00000107984 (ENSEMBL)
DKK1 geneENSG00000107984 (ENSEMBL)
EOMES gene ProteinENSG00000163508 (ENSEMBL)
EOMES geneENSG00000163508 (ENSEMBL)
GATA6 gene ProteinENSG00000141448 (ENSEMBL)
GATA6 geneENSG00000141448 (ENSEMBL)
GSC gene ProteinENSG00000133937 (ENSEMBL)
GSC geneENSG00000133937 (ENSEMBL)
HHEX gene ProteinENSG00000152804 (ENSEMBL)
HHEX geneENSG00000152804 (ENSEMBL)
NANOG ProteinQ9H9S0 (Uniprot-TrEMBL)
NANOGProteinQ9H9S0 (Uniprot-TrEMBL)
POU5F1 ProteinQ01860 (Uniprot-TrEMBL)
POU5F1:NANOG:GATA6 geneComplexR-HSA-2889009 (Reactome)
POU5F1:SOX2:NANOG:CDX2 geneComplexR-HSA-2889022 (Reactome)
POU5F1:SOX2:NANOG:DKK1 geneComplexR-HSA-2888998 (Reactome)
POU5F1:SOX2:NANOG:EOMES geneComplexR-HSA-2889000 (Reactome)
POU5F1:SOX2:NANOG:GSC geneComplexR-HSA-2889033 (Reactome)
POU5F1:SOX2:NANOG:HHEX geneComplexR-HSA-2889020 (Reactome)
POU5F1:SOX2:NANOG:TSC22D1 geneComplexR-HSA-2889006 (Reactome)
POU5F1ProteinQ01860 (Uniprot-TrEMBL)
SOX2 ProteinP48431 (Uniprot-TrEMBL)
SOX2ProteinP48431 (Uniprot-TrEMBL)
TSC22D1 gene ProteinENSG00000102804 (ENSEMBL)
TSC22D1 geneENSG00000102804 (ENSEMBL)

Annotated Interactions

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SourceTargetTypeDatabase referenceComment
CDX2 geneR-HSA-2972979 (Reactome)
DKK1 geneR-HSA-2972977 (Reactome)
EOMES geneR-HSA-2972949 (Reactome)
GATA6 geneR-HSA-2972952 (Reactome)
GSC geneR-HSA-2972948 (Reactome)
HHEX geneR-HSA-2972966 (Reactome)
NANOGR-HSA-2972948 (Reactome)
NANOGR-HSA-2972949 (Reactome)
NANOGR-HSA-2972952 (Reactome)
NANOGR-HSA-2972965 (Reactome)
NANOGR-HSA-2972966 (Reactome)
NANOGR-HSA-2972977 (Reactome)
NANOGR-HSA-2972979 (Reactome)
POU5F1:NANOG:GATA6 geneArrowR-HSA-2972952 (Reactome)
POU5F1:SOX2:NANOG:CDX2 geneArrowR-HSA-2972979 (Reactome)
POU5F1:SOX2:NANOG:DKK1 geneArrowR-HSA-2972977 (Reactome)
POU5F1:SOX2:NANOG:EOMES geneArrowR-HSA-2972949 (Reactome)
POU5F1:SOX2:NANOG:GSC geneArrowR-HSA-2972948 (Reactome)
POU5F1:SOX2:NANOG:HHEX geneArrowR-HSA-2972966 (Reactome)
POU5F1:SOX2:NANOG:TSC22D1 geneArrowR-HSA-2972965 (Reactome)
POU5F1R-HSA-2972948 (Reactome)
POU5F1R-HSA-2972949 (Reactome)
POU5F1R-HSA-2972952 (Reactome)
POU5F1R-HSA-2972965 (Reactome)
POU5F1R-HSA-2972966 (Reactome)
POU5F1R-HSA-2972977 (Reactome)
POU5F1R-HSA-2972979 (Reactome)
R-HSA-2972948 (Reactome) POU5F1 (OCT4), SOX2, and NANOG bind the promoter of the GSC gene (Boyer et al. 2005, Lister et al. 2009) and POU5F1 represses expression (Babaie et al. 2007, Kunarso et al. 2010). GSC represses EVX1 and is required for formation of anterior streak-like progeny in response to Activin (Kalisz et al. 2012). As inferred from mouse, GSC is required for craniofacial development and rib development (Rivera-Perez et al. 1995).
R-HSA-2972949 (Reactome) The EOMES gene is bound by POU5F1 (OCT4) (Boyer et al. 2005, Jin et al. 2007, Jung et al. 2010), SOX2 (Boyer et al. 2005), and NANOG (Boyer et al. 2005, Lister et al. 2009) in embryonic stem cells. POU5F1 (Babaie et al. 2007, Kunarso et al. 2010) and SOX2 (Teo et al. 2011) repress expression, however NANOG enhances expression (Teo et al. 2011). As inferred from mouse, EOMES is required for differentiation of mesoderm (Russ et al. 2000) and directly activates Mesp1, a regulator of cardiovascular differentiation (van den Ameele et al. 2012).
R-HSA-2972952 (Reactome) POU5F1 (OCT4) (Boyer et al. 2005) and NANOG (Boyer et al. 2005, Lister et al. 2009) bind the promoter of the GATA6 gene and POU5F1 represses expression (Babaie et al. 2007, Greber et al. 2007, Kunarso et al. 2010). As inferred from mouse GATA6 is required for endoderm differentiatiation where it directly activates Bmp2 expression (Wang et al. 2011, Rong et al. 2012).
R-HSA-2972965 (Reactome) POU5F1 (OCT4), SOX2, and NANOG bind the promoter of the TSC22D1 gene (Boyer et al. 2005, Lister et al. 2009) and POU5F1 (Babaie et al. 2007, Greber et al. 2007, Kunarso et al. 2010), SOX2 (Greber et al. 2007), and NANOG (Greber et al. 2007) repress expression. TSC22D1 promotes TGFbeta-mediated cardiac myofibroblast differentiation (Yan et al. 2011), regulates hematopoietic cell proliferation (inferred from mouse in Yu et al. 2009), and associates with Smad4 to induce erythroid cell differentiation (inferred from mouse in Choi et al. 2005).
R-HSA-2972966 (Reactome) The HHEX gene is bound by POU5F1 (OCT4) (Boyer et al. 2005), SOX2 (Boyer et al. 2005), and NANOG (Boyer et al. 2005, Lister et al. 2009) and POU5F1 represses expression (Babaie et al. 2007, Kunarso et al. 2010). POU5F1, SOX2, and NANOG bind adjacently (Boyer et al. 2005) therefore POU5F1 and SOX2 may heterodimerize. As inferred from mouse, HHEX is required for hepatic differentiation (Hunter et al. 2007), hematopoiesis (Jayaraman et al. 2000), and endodermal tissues for forebrain and thyroid (Martinez Barbera et al. 2000).
R-HSA-2972977 (Reactome) The DKK1 gene is bound by POU5F1 (OCT4) (Boyer et al. 2005, Jin et al. 2007, Jung et al. 2010), SOX2 (Lister et al. 2009), and NANOG (Boyer et al. 2005, Lister et al. 2009) in embryonic stem cells and POU5F1 (Babaie et al. 2007, Kunarso et al. 2010) represses expression. In mesenchymal stem cells, however, SOX2 appears to activate DKK1 expression (Park et al. 2012). DKK1 is a soluble inhibitor of Wnt signaling that binds the LRP5 receptor (reviewed in Pinzone et al. 2009). As inferred from mouse, DKK1 induces differentiation to neuroectoderm (Kong and Zhang 2009).
R-HSA-2972979 (Reactome) The CDX2 gene is bound by POU5F1 (OCT4) (Boyer et al. 2005, Lister et al. 2009), SOX2 (Lister et al. 2009) and NANOG ( Boyer et al. 2005, Lister et al. 2009) and POU5F1 repress expression of CDX2 (Babaie et al. 2007). CDX2 and T (Brachyury) mediate the differentiation of stem cells induced by BMP (Bernardo et al. 2011).
SOX2R-HSA-2972948 (Reactome)
SOX2R-HSA-2972949 (Reactome)
SOX2R-HSA-2972965 (Reactome)
SOX2R-HSA-2972966 (Reactome)
SOX2R-HSA-2972977 (Reactome)
SOX2R-HSA-2972979 (Reactome)
TSC22D1 geneR-HSA-2972965 (Reactome)
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