BioPAX pathway converted from "POU5F1 (OCT4), SOX2, NANOG, KLF4, PBX1, SMAD2 bind the NANOG promoter" in the Reactome database.POU5F1 (OCT4), SOX2, NANOG, KLF4, PBX1, SMAD2 bind the NANOG promoterPOU5F1 (OCT4), SOX2, NANOG, KLF4, PBX1, SMAD2 bind the NANOG promoterFormation of OCT4:SOX2:NANOG:KLF4:PBX1:SMAD2 Complex at NANOG PromoterKLF4, PBX1, POU5F1 (OCT4), SOX2, and NANOG bind the promoter of the NANOG gene and enhance expression of NANOG (Rodda et al. 2005, Boyer et al. 2005, Babaie et al. 2007, Jin et al. 2007, Chan et al. 2009, Vallier et al. 2009, Jung et al. 2011). In mouse Nanog has been shown to repress its own expression (Fidalgo et al. 2012, Navarro et al. 2012). ZIC3, a NANOG target, also positively regulates NANOG expression, possibly by binding the NANOG promoter and activating transcription (Lim et al. 2007). Activin/Nodal signaling regulates NANOG via SMAD2 and SMAD3 (Brown et al. 2011)Authored: May, B, 2010-11-12Reviewed: Wang, Jianlong, 2014-01-22Edited: May, B, 2010-11-12Reactome DB_ID: 4344631nucleoplasmGO0005654UniProt:O43474 KLF4KLF4EZFKLF4GKLFFUNCTION Transcription factor; can act both as activator and as repressor. Binds the 5'-CACCC-3' core sequence. Binds to the promoter region of its own gene and can activate its own transcription. Regulates the expression of key transcription factors during embryonic development. Plays an important role in maintaining embryonic stem cells, and in preventing their differentiation. Required for establishing the barrier function of the skin and for postnatal maturation and maintenance of the ocular surface. Involved in the differentiation of epithelial cells and may also function in skeletal and kidney development. Contributes to the down-regulation of p53/TP53 transcription.SUBUNIT Interacts with POU5F1/OCT4 and SOX2 (By similarity). Interacts with MUC1 (via the C-terminal domain) (PubMed:17308127). Interacts with MEIS2 isoform 4 and PBX1 isoform PBX1a (PubMed:21746878). Interacts with ZNF296 (By similarity). Interacts with GLIS1 (PubMed:21654807).DOMAIN the 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors.BIOTECHNOLOGY POU5F1/OCT4, SOX2, MYC/c-Myc and KLF4 are the four Yamanaka factors. When combined, these factors are sufficient to reprogram differentiated cells to an embryonic-like state designated iPS (induced pluripotent stem) cells. iPS cells exhibit the morphology and growth properties of ES cells and express ES cell marker genes.SIMILARITY Belongs to the krueppel C2H2-type zinc-finger protein family.Reactomehttp://www.reactome.orgHomo sapiensNCBI Taxonomy9606UniProtO43474Chain Coordinates1EQUAL513EQUALReactome DB_ID: 4525861UniProt:Q9H9S0 NANOGNANOGNANOGFUNCTION Transcription regulator involved in inner cell mass and embryonic stem (ES) cells proliferation and self-renewal. Imposes pluripotency on ES cells and prevents their differentiation towards extraembryonic endoderm and trophectoderm lineages. Blocks bone morphogenetic protein-induced mesoderm differentiation of ES cells by physically interacting with SMAD1 and interfering with the recruitment of coactivators to the active SMAD transcriptional complexes. Acts as a transcriptional activator or repressor. Binds optimally to the DNA consensus sequence 5'-TAAT[GT][GT]-3' or 5'-[CG][GA][CG]C[GC]ATTAN[GC]-3'. Binds to the POU5F1/OCT4 promoter (PubMed:25825768). Able to autorepress its expression in differentiating (ES) cells: binds to its own promoter following interaction with ZNF281/ZFP281, leading to recruitment of the NuRD complex and subsequent repression of expression. When overexpressed, promotes cells to enter into S phase and proliferation.SUBUNIT Interacts with SMAD1 and SALL4. Interacts with ZNF281/ZFP281 (By similarity). Interacts with PCGF1 (PubMed:26687479). Interacts with ESRRB; reciprocally modulates their transcriptional activities (By similarity).TISSUE SPECIFICITY Expressed in testicular carcinoma and derived germ cell tumors (at protein level). Expressed in fetal gonads, ovary and testis. Also expressed in ovary teratocarcinoma cell line and testicular embryonic carcinoma. Not expressed in many somatic organs and oocytes.DEVELOPMENTAL STAGE Expressed in embryonic stem (ES) and carcinoma (EC) cells. Expressed in inner cell mass (ICM) of the blastocyst and gonocytes between 14 and 19 weeks of gestation (at protein level). Not expressed in oocytes, unfertilized oocytes, 2-16 cell embryos and early morula (at protein level). Expressed in embryonic stem cells (ES). Expression decreases with ES differentiation.MISCELLANEOUS Exists an other tandem duplicated non-processed pseudogene (NANOGP1) and 10 other NANOG-related nucleotide sequences located on different chromosomes, all of which are processed pseudogenes lacking introns (NANOGP2 to NANOGP11); except NANOGP8 which is a retrogene.SIMILARITY Belongs to the Nanog homeobox family.UniProtQ9H9S01EQUAL305EQUALReactome DB_ID: 4530451UniProt:P40424 PBX1PBX1PRLPBX1FUNCTION Binds the sequence 5'-ATCAATCAA-3'. Acts as a transcriptional activator of PF4 in complex with MEIS1. Converted into a potent transcriptional activator by the (1;19) translocation. May have a role in steroidogenesis and, subsequently, sexual development and differentiation. Isoform PBX1b as part of a PDX1:PBX1b:MEIS2b complex in pancreatic acinar cells is involved in the transcriptional activation of the ELA1 enhancer; the complex binds to the enhancer B element and cooperates with the transcription factor 1 complex (PTF1) bound to the enhancer A element. Probably in complex with MEIS2, is involved in transcriptional regulation by KLF4. Acts as a transcriptional activator of NKX2-5 and a transcriptional repressor of CDKN2B. Together with NKX2-5, it is required for spleen development through a mechanism that involves CDKN2B repression (By similarity).SUBUNIT Forms a heterodimer with MEIS1 which binds DNA including a cAMP-responsive sequence in CYP17. Also forms heterotrimers with MEIS1 and a number of HOX proteins including HOXA9, HOXD4, HOXD9 and HOXD10. Interacts with PBXIP1 and TLX1. Isoform PBX1a interacts with MEIS2 isoform 4, SP1, SP3 and KLF4. Isoform PBX1b is part of a PDX1:PBX1b:MEIS2b complex; PBX1b recruits Meis2B to the complex. Interacts with FOXC1 (PubMed:15684392). Interacts with MN1 (PubMed:31839203).TISSUE SPECIFICITY Expressed in the kidney. Expressed in the endothelial cells of the glomeruli and interstitium (at protein level) (PubMed:28270404). Expressed in all tissues except in cells of the B and T lineage. Expressed strongly in kidney and brain (PubMed:28270404).DISEASE A chromosomal aberration involving PBX1 is a cause of pre-B-cell acute lymphoblastic leukemia (B-ALL). Translocation t(1;19)(q23;p13.3) with TCF3. TCF3-PBX1 transforms cells by constitutively activating transcription of genes regulated by PBX1 or by other members of the PBX protein family.SIMILARITY Belongs to the TALE/PBX homeobox family.UniProtP404241EQUAL430EQUALReactome DB_ID: 28889721ENSEMBL:ENSG00000111704 NANOGNANOGNANOGENSEMBLENSG00000111704Reactome DB_ID: 89393621UniProt:Q9H334-8 FOXP1FOXP1HSPC215FOXP1FUNCTION Transcriptional repressor (PubMed:18347093, PubMed:26647308). Can act with CTBP1 to synergistically repress transcription but CTPBP1 is not essential (By similarity). Plays an important role in the specification and differentiation of lung epithelium. Acts cooperatively with FOXP4 to regulate lung secretory epithelial cell fate and regeneration by restricting the goblet cell lineage program; the function may involve regulation of AGR2. Essential transcriptional regulator of B-cell development. Involved in regulation of cardiac muscle cell proliferation. Involved in the columnar organization of spinal motor neurons. Promotes the formation of the lateral motor neuron column (LMC) and the preganglionic motor column (PGC) and is required for respective appropriate motor axon projections. The segment-appropriate generation of spinal chord motor columns requires cooperation with other Hox proteins. Can regulate PITX3 promoter activity; may promote midbrain identity in embryonic stem cell-derived dopamine neurons by regulating PITX3. Negatively regulates the differentiation of T follicular helper cells T(FH)s. Involved in maintenance of hair follicle stem cell quiescence; the function probably involves regulation of FGF18 (By similarity). Represses transcription of various pro-apoptotic genes and cooperates with NF-kappa B-signaling in promoting B-cell expansion by inhibition of caspase-dependent apoptosis (PubMed:25267198). Binds to CSF1R promoter elements and is involved in regulation of monocyte differentiation and macrophage functions; repression of CSF1R in monocytes seems to involve NCOR2 as corepressor (PubMed:15286807, PubMed:18799727, PubMed:18347093). Involved in endothelial cell proliferation, tube formation and migration indicative for a role in angiogenesis; the role in neovascularization seems to implicate suppression of SEMA5B (PubMed:24023716). Can negatively regulate androgen receptor signaling (PubMed:18640093). Acts as a transcriptional activator of the FBXL7 promoter; this activity is regulated by AURKA (PubMed:28218735).SUBUNIT Forms homodimers and heterodimers with FOXP2 and FOXP4 (PubMed:25027557). Dimerization is required for DNA-binding. Self-associates (PubMed:26647308). Interacts with CTBP1 (By similarity). Interacts with NCOR2 and AR (PubMed:18347093, PubMed:18640093). Interacts with FOXP2 (PubMed:26647308). Interacts with TBR1 (PubMed:30250039). Interacts with AURKA; this interaction facilitates the phosphorylation of FOXP1, which suppresses the expression of FBXL7 (PubMed:28218735).TISSUE SPECIFICITY Isoform 8 is specifically expressed in embryonic stem cells.INDUCTION By androgen in an isoform-specific manner; expression of isoform 4 is greatly induced.DOMAIN The leucine-zipper is required for dimerization and transcriptional repression.DISEASE A chromosomal aberration involving FOXP1 is found in acute lymphoblastic leukemia. Translocation t(9;3)(p13;p14.1) with PAX5.UniProtQ9H334-81EQUAL693EQUALReactome DB_ID: 4524721UniProt:Q01860 POU5F1POU5F1OCT4OCT3OTF3POU5F1FUNCTION Transcription factor that binds to the octamer motif (5'-ATTTGCAT-3'). Forms a trimeric complex with SOX2 or SOX15 on DNA and controls the expression of a number of genes involved in embryonic development such as YES1, FGF4, UTF1 and ZFP206. Critical for early embryogenesis and for embryonic stem cell pluripotency.SUBUNIT Interacts with PKM. Interacts with WWP2. Interacts with UBE2I and ZSCAN10 (By similarity). Interacts with PCGF1 (PubMed:26687479). Interacts with ESRRB; recruits ESRRB near the POU5F1-SOX2 element in the NANOG proximal promoter; the interaction is DNA independent (By similarity). Interacts with ZNF322 (By similarity). Interacts with MAPK8 and MAPK9; the interaction allows MAPK8 and MAPK9 to phosphorylate POU5F1 on Ser-355 (By similarity). Interacts (when phosphorylated on Ser-355) with FBXW8 (By similarity). Interacts with FBXW4 (By similarity). Interacts with SOX2 and SOX15; binds synergistically with either SOX2 or SOX15 to DNA (By similarity).TISSUE SPECIFICITY Expressed in developing brain. Highest levels found in specific cell layers of the cortex, the olfactory bulb, the hippocampus and the cerebellum. Low levels of expression in adult tissues.DEVELOPMENTAL STAGE Highly expressed in undifferentiated embryonic stem cells and expression decreases gradually after embryoid body (EB) formation.INDUCTION Transcriptional activity is positively regulated by PKM.DOMAIN The POU-specific domain mediates interaction with PKM.PTM Sumoylation enhances the protein stability, DNA binding and transactivation activity. Sumoylation is required for enhanced YES1 expression.PTM Ubiquitinated; undergoes 'Lys-63'-linked polyubiquitination by WWP2 leading to proteasomal degradation.PTM ERK1/2-mediated phosphorylation at Ser-111 promotes nuclear exclusion and proteasomal degradation. Phosphorylation at Thr-235 and Ser-236 decrease DNA-binding and alters ability to activate transcription.BIOTECHNOLOGY POU5F1/OCT4, SOX2, MYC/c-Myc and KLF4 are the four Yamanaka factors. When combined, these factors are sufficient to reprogram differentiated cells to an embryonic-like state designated iPS (induced pluripotent stem) cells. iPS cells exhibit the morphology and growth properties of ES cells and express ES cell marker genes.MISCELLANEOUS Several pseudogenes of POU5F1 have been described on chromosomes 1, 3, 8, 10 and 12. 2 of them, localized in chromosomes 8 and 10, are transcribed in cancer tissues but not in normal ones and may be involved in the regulation of POU5F1 gene activity in carcinogenesis.SIMILARITY Belongs to the POU transcription factor family. Class-5 subfamily.UniProtQ018601EQUAL360EQUALReactome DB_ID: 4522711UniProt:P48431 SOX2SOX2SOX2FUNCTION Transcription factor that forms a trimeric complex with OCT4 on DNA and controls the expression of a number of genes involved in embryonic development such as YES1, FGF4, UTF1 and ZFP206 (By similarity). Binds to the proximal enhancer region of NANOG (By similarity). Critical for early embryogenesis and for embryonic stem cell pluripotency (PubMed:18035408). Downstream SRRT target that mediates the promotion of neural stem cell self-renewal (By similarity). Keeps neural cells undifferentiated by counteracting the activity of proneural proteins and suppresses neuronal differentiation (By similarity). May function as a switch in neuronal development (By similarity).SUBUNIT Interacts with ZSCAN10 (By similarity). Interacts with SOX3 and FGFR1 (By similarity). Interacts with GLIS1 (PubMed:21654807). Interacts with POU5F1; binds synergistically with POU5F1 to DNA (By similarity).PTM Sumoylation inhibits binding on DNA and negatively regulates the FGF4 transactivation.BIOTECHNOLOGY POU5F1/OCT4, SOX2, MYC/c-Myc and KLF4 are the four Yamanaka factors. When combined, these factors are sufficient to reprogram differentiated cells to an embryonic-like state designated iPS (induced pluripotent stem) cells. iPS cells exhibit the morphology and growth properties of ES cells and express ES cell marker genes.UniProtP484311EQUAL317EQUALReactome DB_ID: 2068271SMAD4:p-SMAD2:p-SMAD2 [nucleoplasm]SMAD4:p-SMAD2:p-SMAD2SMAD4:Phospho SMAD2:Phospho SMAD2Reactome DB_ID: 30091852UniProt:Q15796 SMAD2SMAD2SMAD2MADH2MADR2FUNCTION Receptor-regulated SMAD (R-SMAD) that is an intracellular signal transducer and transcriptional modulator activated by TGF-beta (transforming growth factor) and activin type 1 receptor kinases. Binds the TRE element in the promoter region of many genes that are regulated by TGF-beta and, on formation of the SMAD2/SMAD4 complex, activates transcription. May act as a tumor suppressor in colorectal carcinoma. Positively regulates PDPK1 kinase activity by stimulating its dissociation from the 14-3-3 protein YWHAQ which acts as a negative regulator.SUBUNIT Monomer; the absence of TGF-beta. Heterodimer; in the presence of TGF-beta. Forms a heterodimer with co-SMAD, SMAD4, in the nucleus to form the transactivation complex SMAD2/SMAD4. Interacts with AIP1, HGS, PML and WWP1 (By similarity). Interacts with NEDD4L in response to TGF-beta (By similarity). Found in a complex with SMAD3 and TRIM33 upon addition of TGF-beta. Interacts with ACVR1B, SMAD3 and TRIM33. Interacts (via the MH2 domain) with ZFYVE9; may form trimers with the SMAD4 co-SMAD. Interacts with FOXH1, homeobox protein TGIF, PEBP2-alpha subunit, CREB-binding protein (CBP), EP300, SKI and SNW1. Interacts with SNON; when phosphorylated at Ser-465/467. Interacts with SKOR1 and SKOR2. Interacts with PRDM16. Interacts (via MH2 domain) with LEMD3. Interacts with RBPMS. Interacts with WWP1. Interacts (dephosphorylated form, via the MH1 and MH2 domains) with RANBP3 (via its C-terminal R domain); the interaction results in the export of dephosphorylated SMAD3 out of the nucleus and termination of the TGF-beta signaling. Interacts with PDPK1 (via PH domain). Interacts with DAB2; the interactions are enhanced upon TGF-beta stimulation. Interacts with USP15. Interacts with PPP5C. Interacts with ZNF580. Interacts with LDLRAD4 (via the SMAD interaction motif). Interacts (via MH2 domain) with PMEPA1 (via the SMAD interaction motif). Interacts with ZFHX3. Interacts with ZNF451 (PubMed:24324267). Identified in a complex that contains at least ZNF451, SMAD2, SMAD3 and SMAD4 (PubMed:24324267). Interacts weakly with ZNF8 (By similarity). Interacts (when phosphorylated) with RNF111; RNF111 acts as an enhancer of the transcriptional responses by mediating ubiquitination and degradation of SMAD2 inhibitors (By similarity).TISSUE SPECIFICITY Expressed at high levels in skeletal muscle, endothelial cells, heart and placenta.PTM Phosphorylated on one or several of Thr-220, Ser-245, Ser-250, and Ser-255. In response to TGF-beta, phosphorylated on Ser-465/467 by TGF-beta and activin type 1 receptor kinases. TGF-beta-induced Ser-465/467 phosphorylation declines progressively in a KMT5A-dependent manner. Able to interact with SMURF2 when phosphorylated on Ser-465/467, recruiting other proteins, such as SNON, for degradation. In response to decorin, the naturally occurring inhibitor of TGF-beta signaling, phosphorylated on Ser-240 by CaMK2. Phosphorylated by MAPK3 upon EGF stimulation; which increases transcriptional activity and stability, and is blocked by calmodulin. Phosphorylated by PDPK1.PTM In response to TGF-beta, ubiquitinated by NEDD4L; which promotes its degradation. Monoubiquitinated, leading to prevent DNA-binding (By similarity). Deubiquitination by USP15 alleviates inhibition and promotes activation of TGF-beta target genes (PubMed:21947082). Ubiquitinated by RNF111, leading to its degradation: only SMAD2 proteins that are 'in use' are targeted by RNF111, RNF111 playing a key role in activating SMAD2 and regulating its turnover (By similarity).PTM Acetylated on Lys-19 by coactivators in response to TGF-beta signaling, which increases transcriptional activity. Isoform short: Acetylation increases DNA binding activity in vitro and enhances its association with target promoters in vivo. Acetylation in the nucleus by EP300 is enhanced by TGF-beta.SIMILARITY Belongs to the dwarfin/SMAD family.UniProtQ15796O-phospho-L-serine at 465465EQUALO-phospho-L-serine [MOD:00046]O-phospho-L-serine at 467467EQUAL2EQUAL467EQUALReactome DB_ID: 1771031UniProt:Q13485 SMAD4SMAD4SMAD4MADH4DPC4FUNCTION In muscle physiology, plays a central role in the balance between atrophy and hypertrophy. When recruited by MSTN, promotes atrophy response via phosphorylated SMAD2/4. MSTN decrease causes SMAD4 release and subsequent recruitment by the BMP pathway to promote hypertrophy via phosphorylated SMAD1/5/8. Acts synergistically with SMAD1 and YY1 in bone morphogenetic protein (BMP)-mediated cardiac-specific gene expression. Binds to SMAD binding elements (SBEs) (5'-GTCT/AGAC-3') within BMP response element (BMPRE) of cardiac activating regions (By similarity). Common SMAD (co-SMAD) is the coactivator and mediator of signal transduction by TGF-beta (transforming growth factor). Component of the heterotrimeric SMAD2/SMAD3-SMAD4 complex that forms in the nucleus and is required for the TGF-mediated signaling (PubMed:25514493). Promotes binding of the SMAD2/SMAD4/FAST-1 complex to DNA and provides an activation function required for SMAD1 or SMAD2 to stimulate transcription. Component of the multimeric SMAD3/SMAD4/JUN/FOS complex which forms at the AP1 promoter site; required for synergistic transcriptional activity in response to TGF-beta. May act as a tumor suppressor. Positively regulates PDPK1 kinase activity by stimulating its dissociation from the 14-3-3 protein YWHAQ which acts as a negative regulator.SUBUNIT Found in a complex with SMAD1 and YY1 (By similarity). Interacts with CITED2 (By similarity). Monomer; in the absence of TGF-beta activation. Heterodimer; on TGF-beta activation. Composed of two molecules of a C-terminally phosphorylated R-SMAD molecule, SMAD2 or SMAD3, and one molecule of SMAD4 to form the transcriptional active SMAD2/SMAD3-SMAD4 complex. Found in a ternary complex composed of SMAD4, STK11/LKB1 and STK11IP. Interacts with ATF2, COPS5, DACH1, MSG1, SKI, STK11/LKB1, STK11IP and TRIM33. Interacts with ZNF423; the interaction takes place in response to BMP2 leading to activation of transcription of BMP target genes. Interacts with ZNF521; the interaction takes place in response to BMP2 leading to activation of transcription of BMP target genes. Interacts with USP9X. Interacts (via the MH1 and MH2 domains) with RBPMS. Interacts with WWTR1 (via coiled-coil domain). Component of the multimeric complex SMAD3/SMAD4/JUN/FOS which forms at the AP1 promoter site; required for synergistic transcriptional activity in response to TGF-beta. Interacts with CITED1. Interacts with PDPK1 (via PH domain) (By similarity). Interacts with VPS39; this interaction affects heterodimer formation with SMAD3, but not with SMAD2, and leads to inhibition of SMAD3-dependent transcription activation. Interactions with VPS39 and SMAD2 may be mutually exclusive. Interacts with ZC3H3 (By similarity). Interacts (via MH2 domain) with ZNF451 (via N-terminal zinc-finger domains) (PubMed:24324267). Identified in a complex that contains at least ZNF451, SMAD2, SMAD3 and SMAD4 (PubMed:24324267). Interacts weakly with ZNF8 (PubMed:12370310). Interacts with NUP93 and IPO7; translocates SMAD4 to the nucleus through the NPC upon BMP7 stimulation resulting in activation of SMAD4 signaling (PubMed:26878725). Interacts with CREB3L1, the interaction takes place upon TGFB1 induction and SMAD4 acts as CREB3L1 coactivator to induce the expression of genes involved in the assembly of collagen extracellular matrix (PubMed:25310401). Interacts with DLX1 (PubMed:14671321). Interacts with ZBTB7A; the interaction is direct and stimulated by TGFB1 (PubMed:25514493). Interacts with CREBBP; the recruitment of this transcriptional coactivator is negatively regulated by ZBTB7A (PubMed:25514493). Interacts with EP300; the interaction with this transcriptional coactivator is negatively regulated by ZBTB7A (PubMed:25514493). Interacts with HDAC1 (PubMed:25514493). Interacts (via MH2 domain) with ZMIZ1 (via SP-RING-type domain); in the TGF-beta signaling pathway increases the activity of the SMAD3/SMAD4 transcriptional complex (PubMed:16777850).DOMAIN The MH1 domain is required for DNA binding.DOMAIN The MH2 domain is required for both homomeric and heteromeric interactions and for transcriptional regulation. Sufficient for nuclear import.PTM Phosphorylated by PDPK1.PTM Monoubiquitinated on Lys-519 by E3 ubiquitin-protein ligase TRIM33. Monoubiquitination hampers its ability to form a stable complex with activated SMAD2/3 resulting in inhibition of TGF-beta/BMP signaling cascade. Deubiquitination by USP9X restores its competence to mediate TGF-beta signaling.DISEASE SMAD4 variants may be associated with susceptibility to pulmonary hypertension, a disorder characterized by plexiform lesions of proliferating endothelial cells in pulmonary arterioles. The lesions lead to elevated pulmonary arterial pression, right ventricular failure, and death. The disease can occur from infancy throughout life and it has a mean age at onset of 36 years. Penetrance is reduced. Although familial pulmonary hypertension is rare, cases secondary to known etiologies are more common and include those associated with the appetite-suppressant drugs.SIMILARITY Belongs to the dwarfin/SMAD family.UniProtQ134851EQUAL552EQUALReactome Database ID Release 75206827Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=206827ReactomeR-HSA-2068272Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-206827.2Reactome DB_ID: 4804631POU5F1:SOX2:NANOG:KLF4:PBX1:SMAD2:FOXP1-ES:NANOG gene [nucleoplasm]POU5F1:SOX2:NANOG:KLF4:PBX1:SMAD2:FOXP1-ES:NANOG geneOCT4:SOX2:NANOG:KLF4:PBX1:SMAD2:FOXP1-ES:NANOG geneReactome DB_ID: 45304511EQUAL430EQUALReactome DB_ID: 45258611EQUAL305EQUALReactome DB_ID: 43446311EQUAL513EQUALReactome DB_ID: 28889721Reactome DB_ID: 893936211EQUAL693EQUALReactome DB_ID: 45247211EQUAL360EQUALReactome DB_ID: 45227111EQUAL317EQUALReactome DB_ID: 2068271Reactome Database ID Release 75480463Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=480463ReactomeR-HSA-4804632Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-480463.2Reactome Database ID Release 75480204Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=480204ReactomeR-HSA-4802042Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-480204.217267691Pubmed2007Zic3 is required for maintenance of pluripotency in embryonic stem cellsLim, LSLoh, YHZhang, WLi, YChen, XWang, YBakre, MNg, HHStanton, LWMol Biol Cell 18:1348-5817068183Pubmed2007Analysis of Oct4-dependent transcriptional networks regulating self-renewal and pluripotency in human embryonic stem cellsBabaie, YHerwig, RGreber, BBrink, TCWruck, WGroth, DLehrach, HBurdon, TAdjaye, JStem Cells 25:500-1015860457Pubmed2005Transcriptional regulation of nanog by OCT4 and SOX2Rodda, DJChew, JLLim, LHLoh, YHWang, BNg, HHRobson, PJ Biol Chem 280:24731-719688839Pubmed2009Signaling pathways controlling pluripotency and early cell fate decisions of human induced pluripotent stem cellsVallier, LudovicTouboul, ThomasBrown, StephanieCho, CandyBilican, BiladaAlexander, MorganCedervall, JessicaChandran, SiddharthanAhrlund-Richter, LarsWeber, AnnePedersen, Roger AStem Cells 27:2655-6621630377Pubmed2011Activin/Nodal signaling controls divergent transcriptional networks in human embryonic stem cells and in endoderm progenitorsBrown, StephanieTeo, AdrianPauklin, SiimHannan, NicholasCho, Candy H-HLim, BingVardy, LeahDunn, N RayTrotter, MatthewPedersen, RogerVallier, LudovicStem Cells 29:1176-8523178592Pubmed2012OCT4/SOX2-independent Nanog autorepression modulates heterogeneous Nanog gene expression in mouse ES cellsNavarro, PabloFestuccia, NicolaColby, DouglasGagliardi, AlessiaMullin, Nicholas PZhang, WenshengKarwacki-Neisius, ViolettaOsorno, RodrigoKelly, DavidRobertson, MoragChambers, IanEMBO J. 31:4547-6217567999Pubmed2007Identification of an OCT4 and SRY regulatory module using integrated computational and experimental genomics approachesJin, Victor XO'Geen, HenrietteIyengar, SushmaGreen, RolandFarnham, Peggy JGenome Res. 17:807-1722988117Pubmed2012Zfp281 mediates Nanog autorepression through recruitment of the NuRD complex and inhibits somatic cell reprogrammingFidalgo, MiguelFaiola, FrancescoPereira, Carlos-FilipeDing, JunjunSaunders, ArvenGingold, JulianSchaniel, ChristophLemischka, Ihor RSilva, José C RWang, JianlongProc. Natl. Acad. Sci. U.S.A. 109:16202-719522013Pubmed2009KLF4 and PBX1 directly regulate NANOG expression in human embryonic stem cellsChan, KKZhang, JChia, NYChan, YSSim, HSTan, KSOh, SKNg, HHChoo, ABStem Cells 27:2114-2520505756Pubmed2010A data integration approach to mapping OCT4 gene regulatory networks operative in embryonic stem cells and embryonal carcinoma cellsJung, MPeterson, HChavez, LKahlem, PLehrach, HVilo, JAdjaye, JPLoS One 5:e1070916153702Pubmed2005Core transcriptional regulatory circuitry in human embryonic stem cellsBoyer, LALee, TICole, MFJohnstone, SELevine, SSZucker, JPGuenther, MGKumar, RMMurray, HLJenner, RGGifford, DKMelton, DAJaenisch, RYoung, RACell 122:947-56