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

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  <Comment Source="WikiPathways-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).
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  <Comment Source="Reactome Author">Reactome Author: May, Bruce</Comment>
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    <Comment Source="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.</Comment>
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    <Comment Source="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).</Comment>
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    <Comment Source="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).</Comment>
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    <Comment Source="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).</Comment>
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    <Comment Source="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).</Comment>
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    <Comment Source="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).</Comment>
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    <Comment Source="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).</Comment>
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    <Comment Source="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).</Comment>
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