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

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3, 15, 18, 19, 21...2, 14, 20-23, 304, 13, 21, 23, 24, 28...12, 20, 21, 239, 16, 20, 21, 23...6, 10, 20-23, 25...7, 8, 11, 17, 20...1, 5, 20, 21, 23...nucleoplasmNANOG DKK1 gene TSC22D1 gene NANOG POU5F1:NANOG:GATA6geneSOX2SOX2 NANOG CDX2 geneSOX2 GATA6 geneNANOG EOMES geneCDX2 gene TSC22D1 genePOU5F1:SOX2:NANOG:GSC genePOU5F1 GSC gene POU5F1 POU5F1 POU5F1 POU5F1:SOX2:NANOG:EOMES geneSOX2 POU5F1:SOX2:NANOG:DKK1 geneGATA6 gene POU5F1:SOX2:NANOG:HHEX geneNANOG POU5F1 POU5F1:SOX2:NANOG:CDX2 geneHHEX geneNANOG POU5F1SOX2 SOX2 POU5F1 HHEX gene POU5F1 NANOG DKK1 geneEOMES gene GSC geneNANOGPOU5F1:SOX2:NANOG:TSC22D1 geneSOX2 8, 20, 22, 2320, 2320, 2320, 2320, 23, 308, 20, 22, 2320, 23


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). View original pathway at Reactome.

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Pathway is converted from Reactome ID: 2892245
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Reactome version: 75
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Reactome Author: May, Bruce

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Bibliography

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  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
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  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
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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 geneGeneProductENSG00000165556 (Ensembl)
DKK1 gene ProteinENSG00000107984 (Ensembl)
DKK1 geneGeneProductENSG00000107984 (Ensembl)
EOMES gene ProteinENSG00000163508 (Ensembl)
EOMES geneGeneProductENSG00000163508 (Ensembl)
GATA6 gene ProteinENSG00000141448 (Ensembl)
GATA6 geneGeneProductENSG00000141448 (Ensembl)
GSC gene ProteinENSG00000133937 (Ensembl)
GSC geneGeneProductENSG00000133937 (Ensembl)
HHEX gene ProteinENSG00000152804 (Ensembl)
HHEX geneGeneProductENSG00000152804 (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 geneGeneProductENSG00000102804 (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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