POU5F1 (OCT4), SOX2, NANOG activate genes related to proliferation (Homo sapiens)

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17, 18, 20, 23, 26...1, 12, 14, 17, 20...14, 17, 20, 2717, 233, 17, 20, 27, 35...7, 9, 13, 17, 20...4, 17, 20, 3817, 20, 23, 319, 15, 17, 34, 35, 42...4, 8, 9, 16, 17, 22...14, 17, 20, 35, 5014, 17, 20, 3510, 17, 20, 24, 27...2, 5, 6, 17, 20...14, 17, 20, 35, 38...12, 14, 17, 20, 27...11, 17-21, 33...cytosolnucleoplasmSALL1EPHA1 geneSTAT3 geneNR6A1(GCNF):TDGF1geneNANOG N-aspartyl-glycosylphosphatidylinositolethanolamine-TDGF1(31-188)POU5F1:SOX2:NANOG:FGF2 geneNANOG POU5F1:SOX2:NANOG:ZIC3 geneSALL1 gene NANOG SALL4:SALL1 geneZIC3 gene SALL1 geneSOX2 NR6A1-1 TDGF1 gene POU5F1:SOX2:NANOG:TDGF1 geneFOXD3 gene POU5F1 SOX2 SALL1 gene FOXD3 geneSOX2 POU5F1EPHA1ZIC3 geneFGF2 gene SOX2 SOX2 POU5F1 NANOG POU5F1 TDGF1 gene POU5F1:SOX2:NANOG:EPHA1 geneDPPA4 gene DPPA4DPPA4 geneNANOG SOX2NANOGZIC3POU5F1:SOX2:NANOG:SALL1 geneNANOG POU5F1 POU5F1 NANOG FGF2(10-155)FGF2 geneFOXD3STAT3 gene POU5F1:SOX2:NANOG:DPPA4 genePOU5F1 TDGF1 genePOU5F1 SOX2 POU5F1 POU5F1:SOX2:NANOG:STAT3 geneSOX2 SOX2 STAT3SALL4 POU5F1:SOX2:NANOG:FOXD3 geneNANOG EPHA1 gene 12, 14, 17, 27, 38...14, 171, 12, 14, 17, 5014, 17, 5014, 17, 384617, 3814, 17, 38


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 and repress another subset (Kim et al. 2006, Matoba et al. 2006, Player et al. 2006, Babaie et al. 2007). The targets listed in this module are those that have been described as composing activated genes in the core transcriptional network of pluripotent stem cells (Assou et al. 2007, Chavez et al. 2009, Jung et al. 2010). Inferences from mouse to human have been made with caution because of significant differences between the two species (Ginis et al. 2004). View original pathway at:Reactome.

Comments

Reactome-Converter 
Pathway is converted from Reactome ID: 2892247
Reactome-version 
Reactome version: 61
Reactome Author 
Reactome Author: May, Bruce

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Bibliography

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History

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CompareRevisionActionTimeUserComment
101455view11:32, 1 November 2018ReactomeTeamreactome version 66
100993view21:11, 31 October 2018ReactomeTeamreactome version 65
100529view19:45, 31 October 2018ReactomeTeamreactome version 64
100076view16:28, 31 October 2018ReactomeTeamreactome version 63
99627view15:01, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
99233view12:44, 31 October 2018ReactomeTeamreactome version 62
93996view13:50, 16 August 2017ReactomeTeamreactome version 61
93605view11:28, 9 August 2017ReactomeTeamreactome version 61
88106view09:56, 26 July 2016RyanmillerOntology Term : 'transcription pathway' added !
88105view09:53, 26 July 2016RyanmillerOntology Term : 'regulatory pathway' added !
86712view09:24, 11 July 2016ReactomeTeamreactome version 56
83109view09:59, 18 November 2015ReactomeTeamVersion54
81441view12:58, 21 August 2015ReactomeTeamNew pathway

External references

DataNodes

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NameTypeDatabase referenceComment
DPPA4 gene ProteinENSG00000121570 (Ensembl)
DPPA4 geneGeneProductENSG00000121570 (Ensembl)
DPPA4ProteinQ7L190 (Uniprot-TrEMBL)
EPHA1 gene ProteinENSG00000146904 (Ensembl)
EPHA1 geneGeneProductENSG00000146904 (Ensembl)
EPHA1ProteinP21709 (Uniprot-TrEMBL)
FGF2 gene ProteinENSG00000138685 (Ensembl)
FGF2 geneGeneProductENSG00000138685 (Ensembl)
FGF2(10-155)ProteinP09038 (Uniprot-TrEMBL)
FOXD3 gene ProteinENSG00000187140 (Ensembl)
FOXD3 geneGeneProductENSG00000187140 (Ensembl)
FOXD3ProteinQ9UJU5 (Uniprot-TrEMBL)
N-aspartyl-glycosylphosphatidylinositolethanolamine-TDGF1(31-188)ProteinP13385 (Uniprot-TrEMBL)
NANOG ProteinQ9H9S0 (Uniprot-TrEMBL)
NANOGProteinQ9H9S0 (Uniprot-TrEMBL)
NR6A1(GCNF):TDGF1 geneComplexR-HSA-2892230 (Reactome)
NR6A1-1 ProteinQ15406-1 (Uniprot-TrEMBL)
POU5F1 ProteinQ01860 (Uniprot-TrEMBL)
POU5F1:SOX2:NANOG:DPPA4 geneComplexR-HSA-6800114 (Reactome)
POU5F1:SOX2:NANOG:EPHA1 geneComplexR-HSA-2889014 (Reactome)
POU5F1:SOX2:NANOG:FGF2 geneComplexR-HSA-2889015 (Reactome)
POU5F1:SOX2:NANOG:FOXD3 geneComplexR-HSA-2889032 (Reactome)
POU5F1:SOX2:NANOG:SALL1 geneComplexR-HSA-2889029 (Reactome)
POU5F1:SOX2:NANOG:STAT3 geneComplexR-HSA-2889003 (Reactome)
POU5F1:SOX2:NANOG:TDGF1 geneComplexR-HSA-2889018 (Reactome)
POU5F1:SOX2:NANOG:ZIC3 geneComplexR-HSA-2889030 (Reactome)
POU5F1ProteinQ01860 (Uniprot-TrEMBL)
SALL1 gene ProteinENSG00000103449 (Ensembl)
SALL1 geneGeneProductENSG00000103449 (Ensembl)
SALL1ProteinQ9NSC2 (Uniprot-TrEMBL)
SALL4 ProteinQ9UJQ4 (Uniprot-TrEMBL)
SALL4:SALL1 geneComplexR-HSA-2889010 (Reactome)
SOX2 ProteinP48431 (Uniprot-TrEMBL)
SOX2ProteinP48431 (Uniprot-TrEMBL)
STAT3 gene ProteinENSG00000168610 (Ensembl)
STAT3 geneGeneProductENSG00000168610 (Ensembl)
STAT3ProteinP40763 (Uniprot-TrEMBL)
TDGF1 gene ProteinENSG00000241186 (Ensembl)
TDGF1 geneGeneProductENSG00000241186 (Ensembl)
ZIC3 gene ProteinENSG00000156925 (Ensembl)
ZIC3 geneGeneProductENSG00000156925 (Ensembl)
ZIC3ProteinO60481 (Uniprot-TrEMBL)

Annotated Interactions

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SourceTargetTypeDatabase referenceComment
DPPA4 geneR-HSA-452701 (Reactome)
DPPA4 geneR-HSA-6800120 (Reactome)
DPPA4ArrowR-HSA-452701 (Reactome)
EPHA1 geneR-HSA-2972967 (Reactome)
EPHA1 geneR-HSA-480509 (Reactome)
EPHA1ArrowR-HSA-480509 (Reactome)
FGF2 geneR-HSA-2972960 (Reactome)
FGF2 geneR-HSA-480515 (Reactome)
FGF2(10-155)ArrowR-HSA-480515 (Reactome)
FOXD3 geneR-HSA-2972964 (Reactome)
FOXD3 geneR-HSA-452750 (Reactome)
FOXD3ArrowR-HSA-452750 (Reactome)
N-aspartyl-glycosylphosphatidylinositolethanolamine-TDGF1(31-188)ArrowR-HSA-452338 (Reactome)
NANOGR-HSA-2972956 (Reactome)
NANOGR-HSA-2972960 (Reactome)
NANOGR-HSA-2972962 (Reactome)
NANOGR-HSA-2972964 (Reactome)
NANOGR-HSA-2972967 (Reactome)
NANOGR-HSA-2972975 (Reactome)
NANOGR-HSA-2972978 (Reactome)
NANOGR-HSA-6800120 (Reactome)
NR6A1(GCNF):TDGF1 geneTBarR-HSA-452338 (Reactome)
POU5F1:SOX2:NANOG:DPPA4 geneArrowR-HSA-452701 (Reactome)
POU5F1:SOX2:NANOG:DPPA4 geneArrowR-HSA-6800120 (Reactome)
POU5F1:SOX2:NANOG:EPHA1 geneArrowR-HSA-2972967 (Reactome)
POU5F1:SOX2:NANOG:EPHA1 geneArrowR-HSA-480509 (Reactome)
POU5F1:SOX2:NANOG:FGF2 geneArrowR-HSA-2972960 (Reactome)
POU5F1:SOX2:NANOG:FGF2 geneArrowR-HSA-480515 (Reactome)
POU5F1:SOX2:NANOG:FOXD3 geneArrowR-HSA-2972964 (Reactome)
POU5F1:SOX2:NANOG:FOXD3 geneArrowR-HSA-452750 (Reactome)
POU5F1:SOX2:NANOG:SALL1 geneArrowR-HSA-2972975 (Reactome)
POU5F1:SOX2:NANOG:SALL1 geneArrowR-HSA-452958 (Reactome)
POU5F1:SOX2:NANOG:STAT3 geneArrowR-HSA-2972956 (Reactome)
POU5F1:SOX2:NANOG:STAT3 geneArrowR-HSA-452515 (Reactome)
POU5F1:SOX2:NANOG:TDGF1 geneArrowR-HSA-2972962 (Reactome)
POU5F1:SOX2:NANOG:TDGF1 geneArrowR-HSA-452338 (Reactome)
POU5F1:SOX2:NANOG:ZIC3 geneArrowR-HSA-2972978 (Reactome)
POU5F1:SOX2:NANOG:ZIC3 geneArrowR-HSA-480470 (Reactome)
POU5F1R-HSA-2972956 (Reactome)
POU5F1R-HSA-2972960 (Reactome)
POU5F1R-HSA-2972962 (Reactome)
POU5F1R-HSA-2972964 (Reactome)
POU5F1R-HSA-2972967 (Reactome)
POU5F1R-HSA-2972975 (Reactome)
POU5F1R-HSA-2972978 (Reactome)
POU5F1R-HSA-6800120 (Reactome)
R-HSA-2972956 (Reactome) The STAT3 gene is bound by POU5F1 (OCT4) (Boyer et al. 2005, Lister et al. 2009, Jung et al. 2010), SOX2 (Boyer et al. 2005, Lister et al. 2009), and NANOG (Boyer et al. 2005, Lister et al. 2009) and POU5F1 (Babaie et al. 2007, Greber et al. 2007), SOX2 (Greber et al. 2007), and NANOG (Greber et al. 2007) activate expression.
R-HSA-2972960 (Reactome) The FGF2 gene is bound by POU5F1 (OCT4) (Boyer et al. 2005), SOX2 (Boyer et al. 2005, Lister et al. 2009), NANOG (Boyer et al. 2005, Lister et al. 2009) and expression of the FGF2 mRNA is activated by POU5F1 (Babaie et al. 2007, Greber et al. 2007) and SOX2 (Greber et al. 2007).
R-HSA-2972962 (Reactome) The TDGF1 (CRIPTO) gene is bound by POU5F1 (OCT4) (Boyer et al. 2005, Jin et al. 2007, Tantin et al. 2008, Jung et al. 2010, Watanabe et al. 2010), SOX2 (Boyer et al. 2005, Lister et al. 2009), and NANOG (Boyer et al. 2005, Lister et al. 2009, Watanabe et al. 2010). POU5F1 (Babaie et al. 2007, Greber et al. 2007, Watanabe et al. 2010), SOX2 (Greber et al. 2007), and NANOG (Greber et al. 2007, Watanabe et al. 2010) activate expression. Embryonal carcinoma cells that express higher levels of TDGF1 are more tumorigenic (Watanabe et al. 2010).
R-HSA-2972964 (Reactome) The FOXD3 gene is bound by POU5F1 (OCT4) (Boyer et al. 2005, Jung et al. 2010), SOX2 (Boyer et al. 2005, Lister et al. 2009), and NANOG (Boyer et al. 2005, Lister et al. 2009) and POU5F1 activates expression (Babaie et al. 2007, Kunarso et al. 2010).
R-HSA-2972967 (Reactome) The EPHA1 gene is bound by POU5F1 (OCT4) (Boyer et al. 2005, Jin et al. 2007, Jung et al. 2010, Kunarso et al. 2010, Goke et al. 2011), SOX2 (Boyer et al. 2005, Lister et al. 2009), NANOG (Boyer et al. 2005, Lister et al. 2009, Kunarso et al. 2010) and expression of the EPHA1 mRNA is activated by POU5F1 (Babaie et al. 2007, Greber et al. 2007, Kunarso et al. 2010), SOX2 (Greber et al. 2007), and NANOG (Greber et al. 2007).
R-HSA-2972975 (Reactome) POU5F1 (OCT4), SOX2, and NANOG bind the promoter of the SALL1 gene (Boyer et al. 2005, Yang et al. 2010) and activate expression (Babaie et al. 2007). SALL4 binds the SALL1 promoter and represses expression thus making SALL4 and POU5F1 antagonistic (Yang et al. 2010).
R-HSA-2972978 (Reactome) POU5F1 (OCT4), SOX2, and NANOG bind the promoter of the ZIC3 gene (Boyer et al. 2005, Lister et al. 2009) and POU5F1 (Babaie et al. 2007, Greber et al. 2007) and SOX2 (Greber et al. 2007) activate expression. In mouse, Zic3 binds the Nanog promoter and activates transcription, thus forming a positive feedback loop (Lim et al. 2010).
R-HSA-452338 (Reactome) The TDGF1 (CRIPTO) gene is transcribed to yield mRNA and the mRNA is translated to yield protein. TDGF1/CRIPTO is expressed in embryonic stem cells (Adewumi et al. 2007, Li et al. 2006, Assou et al. 2009). GCNF (NR6A1) binds to the promoter of the TDGF1 (CRIPTO) gene and downregulates expression of TDGF1 (CRIPTO) during differentiation (Hentschke et al. 2006). POU5F1 (OCT4), SOX2, and NANOG bind the promoter of the TDGF1 gene and enhance transcription (Babaie et al. 2007, Greber et al. 2007, Watanabe et al. 2010). SOX2 binds the TDGF1 promoter adjacent to POU5F1 (Boyer et al. 2005). TDGF1 is a marker of undifferentiated stem cells (reviewed in Bianco et al. 2010, de Castro et al. 2010). Expression of TDGF1 is associated with tumorigenesis (Ciardiello et al. 1991).
R-HSA-452515 (Reactome) The STAT3 gene is transcribed to yield mRNA and the mRNA is translated to yield protein. STAT3 is expressed in embryonic stem cells (Schuringa et al. 2002, Fong et al. 2008). POU5F1 (OCT4), SOX2, and NANOG bind the promoter of the STAT3 gene and enhance transcription (Boyer et al. 2005, Greber et al. 2007, Fong et al. 2008). The binding site of POU5F1 is adjacent to the binding site of SOX2 in the STAT3 promoter (Boyer et al. 2005). Signaling by LIF via STAT3 in murine but not human stem cells is sufficient to prevent differentiation (Schuringa et al. 2002, Humphrey et al. 2004, Daheron et al. 2004).
R-HSA-452701 (Reactome) DPPA4 is expressed in pluripotent stem cells. The promoter of the DPPA4 gene binds OCT4 (POU5F1), SOX2, and NANOG (Player et al. 2006, Boyer et al. 2007, inferred from mouse homologs in Chakravarthy et al. 2008). OCT4 Knockdown experiments show OCT4 enhances expression of DPPA4 (Babaie et al. 2007).
R-HSA-452750 (Reactome) The Forkhead box protein D3 (FOXD3) gene is transcribed and translated to yield FOXD3 protein. FOXD3 is expressed in blastomeres of the inner cell mass (Galan et al. 2010, Arduini et al. 2012). POU5F1 (OCT4), SOX2, and NANOG bind the promoter of the FOXD3 gene and POU5F1 enhances transcription (Babaie et al. 2007, Kunarso et al. 2010). The binding site of POU5F1 is not adjacent to the binding site of SOX2 on the FOXD3 promoter (Boyer et al. 2005). FOXD3 is a molecular marker of stem cells (Calloni et al.2013) and a balance of FOXD3 expression is required to maintain pluripotency (Arduini and Brinvalou 2012, inferred from mouse in Liu and Labosky 2008).
R-HSA-452958 (Reactome) The SALL1 gene is transcribed to yield mRNA and the mRNA is translated to yield protein. SALL1 mRNA and protein are expressed in pituitary, adrenal cortex and the placenta in addition to kidney, testicular, and ovarian cells (Ma et al 2002, Chai et al. 2006). Mutations in SALL1 cause Townes-Brocks syndrome. The protein localizes to pericentric heterochromatin (Netzer et al. 2001). POU5F1 (OCT4), SOX2, and NANOG bind the promoter of the SALL1 gene and enhance transcription (Boyer et al. 2005, Fong et al. 2008). SOX2 binds a site in the SALL1 promoter adjacent to the site bound by POU5F1 (Boyer et al. 2005). SALL4 binds the promoter of the SALL1 gene and represses transcription by associating with Mi-2 (NuRD) repressor complex (Lu et al. 2009, Yang et al. 2010).
R-HSA-480470 (Reactome) The ZIC3 gene is transcribed to yield mRNA and the mRNA is translated to yield protein. POU5F1 (OCT4), SOX2, and NANOG bind the promoter of the ZIC3 gene and POU5F1 (Babaie et al. 2007, Greber et al. 2007) and SOX2 (Greber et al. 2007) enhances transcription. SOX2 binds adjacent to POU5F1 on the ZIC3 promoter (Boyer et al. 2005). ZIC3 is expressed in embryonic stem cells where it maintains pluripotency (Lim et al. 2007). As inferred from mouse, ZIC3 is involved in correct patterning during gastrulation (Ware et al. 2006) and mutations in ZIC3 cause heterotaxy in humans (Gebbia et al. 1997, Ware et al. 2004).
R-HSA-480509 (Reactome) The EPHA1 gene is transcribed to yield mRNA and the mRNA is translated to yield protein. EPHA1 is expressed most highly in epidermis of skin and is downregulated in nonmelanomal skin cancers (Hafner et al. 2006). EPHA1 is expressed at lower levels in liver, colon, small intestine, bladder, kidney, prostate, and thymus (Hafner et al. 2006). POU5F1 (OCT4), SOX2, and NANOG bind the promoter of the EPHA1 gene and OCT4 (Babaie et al. 2007, Greber et al. 2007, Kunarso et al. 2010), SOX2 (Greber et al. 2007) and NANOG (Greber et al. 2007) enhance transcription. The binding site of POU5F1 is adjacent to the binding site of SOX2 on the promoter of EPHA1 (Boyer et al. 2005). Expression and kinase activity of EPHA1 correlate with maintenance of pluripotency (Son et al. 2013).
R-HSA-480515 (Reactome) The FGF2 (bFGF) gene is transcribed to yield mRNA and the mRNA is translated to yield protein. FGF2 is expressed in most tissues including kidney, skin, liver, ureter, and vasculature (Hughes and Hall 1993). FGF2 is expressed in about 35% of tumor lines (Chandler et al. 1999). POU5F1 (OCT4), SOX2, and NANOG bind the promoter of the FGF2 gene and POU5F1 (Babaie et al. 2007, Greber et al. 2007) and SOX2 (Greber et al. 2007) enhance transcription. The binding site of POU5F1 is adjacent to the binding site of SOX2 on the FGF2 promoter (Boyer et al. 2005). FGF2 maintains human embryonic stem cells in an undifferentiated state (Dvorak et al. 2005, Eiselleova et al. 2009).
R-HSA-6800120 (Reactome) POU5F1, SOX2, and NANOG bind the promoter of the DPPA4 gene and activate transcription of DPPA4 (Player et al. 2006, Boyer et al. 2007).
SALL1 geneR-HSA-2972975 (Reactome)
SALL1 geneR-HSA-452958 (Reactome)
SALL1ArrowR-HSA-452958 (Reactome)
SALL4:SALL1 geneTBarR-HSA-452958 (Reactome)
SOX2R-HSA-2972956 (Reactome)
SOX2R-HSA-2972960 (Reactome)
SOX2R-HSA-2972962 (Reactome)
SOX2R-HSA-2972964 (Reactome)
SOX2R-HSA-2972967 (Reactome)
SOX2R-HSA-2972975 (Reactome)
SOX2R-HSA-2972978 (Reactome)
SOX2R-HSA-6800120 (Reactome)
STAT3 geneR-HSA-2972956 (Reactome)
STAT3 geneR-HSA-452515 (Reactome)
STAT3ArrowR-HSA-452515 (Reactome)
TDGF1 geneR-HSA-2972962 (Reactome)
TDGF1 geneR-HSA-452338 (Reactome)
ZIC3 geneR-HSA-2972978 (Reactome)
ZIC3 geneR-HSA-480470 (Reactome)
ZIC3ArrowR-HSA-480470 (Reactome)
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