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FLASH GENE
Symbol POU5F1 contributors: mct/ - updated : 11-09-2016
HGNC name POU class 5 homeobox 1
HGNC id 9221
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • N-terminal transactivation domain required for activation of Lefty1 expression
  • a homeobox DNA-binding domain
  • a POU (Pit, Oct, Unc) specific domain
  • a'NORE' (N-Oct-3 responsive element) comprising the 14 bp sequence element TNNRTAAATAATRN, involved in homodimerization
  • mono polymer homomer , heteromer , dimer
    HOMOLOGY
    interspecies homolog to rattus Pou5f1 (86.4pc)
    homolog to murine Pou5f1 (86.1pc)
    homolog to zebrafish pou5f1
    intraspecies paralog to SLC22A1
    Homologene
    FAMILY
  • POU (Pit/OCT/Unc) family of transcription factors
  • class-5 subfamily
  • CATEGORY transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus
    text
  • nucleocytoplasmic shuttling protein
  • basic FUNCTION
  • prime candidate for an early developmental control gene
  • involved in regulation of pluripotency during normal development and is detectable in embryonic stem and germ cells
  • potential transcriptional activator for fibroblast growth factor-4 (FGF4) in breast cancer cells
  • is essential for a normal post-stress transcriptional response
  • may be an oncogenic factor in GCTs
  • inhibitory effect of POU5F1 is mediated by transactivation domains
  • controlling cell cycle progression of embryonic stem cells and repressing CDKN1A
  • transcription factor, playing an important role in maintaining the pluripotency and self-renewal of embryonic stem (ES) cells
  • involved in embryonic stem cell differentiation
  • POU5F1 and TSIX are crucial toward achieving the balance of multiple XIST activators and repressors
  • acts as a transcriptional activator during dorsoventral patterning
  • POU5F1, SOX2, and NANOG cooperate with a wide array of cofactors to orchestrate an embryonic stem (ES) cell-specific gene expression program that forms the molecular basis of pluripotency
  • important roles of POU5F1 and NANOG in maintaining mesenchymal stem cells properties
  • necessary and sufficient function of POU5F1 in promoting pluripotency is to activate specific target genes
  • is essential for maintaining pluripotency in embryonic stem cells (ESCs)
  • POU5F1-gene regulatory network thus provides a connection between eggs, early preimplantation embryos and embryonic stem cells
  • critical role in both maintenance of the undifferentiated state of embryonic stem (ES) cells and in the reprogramming of somatic cells to induced pluripotent stem cells
  • to function as a transcription factor that maintains the undifferentiated state of ES cells, only has to stay transiently in the nucleus
  • plays distinct roles in the self-renewal of ES cells and in somatic cell reprogramming
  • a defined POU5F1 level controls the establishment of naive pluripotency as well as commitment to all embryonic lineages
  • upon the induction of ESC differentiation, OTX2 alone or in combination with POU5F1 engages new enhancers, which are silent in undifferentiated ESCs
  • CELLULAR PROCESS nucleotide, transcription, regulation
    PHYSIOLOGICAL PROCESS development
    text morphogenesis
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA binding to the octamer motif 5'-ATTTGCAT-3'
    RNA
    small molecule
    protein
  • direct target of LEFTY1 (cooperation of Kruppel-like factor 4 (KLF4) cooperates with POU5F1 and and SOX2 to activate LEFTY1 expression)
  • ZNF281 directly activate NANOG expression by binding to a site in the promoter in very close proximity to the POU5F1 and SOX2 binding sites
  • interacting with KPNA2
  • POU5F1 and WDR5 are partners in transcriptional regulation
  • acts as a transcriptional suppressor of MYOD1 gene expression through its interaction with the upstream enhancer region
  • involved in the synergistic activation of NANOG, that requires a multisubunit stem cell coactivator complex (SCC)
  • SOX2 cooperates with POU5F1 to activate downstream target genes by binding to Oct-Sox enhancers
  • NR5A2 acts as a transcriptional activator in the regulation of POU5F1 gene expression through the cooperative interaction with three binding sites directly or/and indirectly
  • MBD6 was detected as an POU5F1 regulatory gene
  • CDK1 and POU5F1 interplay to inhibit ES cell differentiation into trophectoderm and thereby maintain stemness
  • ITCH interacts with and targets pluripotency-associated transcription factor POU5F1 for ubiquitination
  • can upregulate BIRC5 and CCND1 expression by increasing their promoter activity, and these factors collusively promotes hepatocellular carcinoma cell proliferation
  • genomic redistribution of POU5F1 by alternative partnering with SOX2 and SOX17 is a fundamental regulatory event of endodermal specification
  • its post-translational modifications form a positive feedback loop, which promote AKT1 activation and interaction with HMGB2 and the SET Complex
  • chromatin regulators EP300, KDM5A, KDM6A and KDM6B cooperate with KLF4 in promoting the transcription of POU5F1
  • TAF4B cooperates with POU5F1 to regulate a subset of genes in ESC, whereas TAF4 is required for later embryonic developmental stages
  • regulates the proper splicing of transcripts encoding for pluripotency regulators such as POU5F1, PRDM14, E4F1 and MED24
  • DIDO1 could target to the loci of pluripotency factors such as NANOG and POU5F1 and positively regulate their expression
  • oncogenic factor ETV4 regulates POU5F1 gene expression as a transcriptional activator
  • affects the metastatic potential of breast cancer cells through RND1-mediated effects that influence cell motility and E-cadherin expression
  • TRIM32 modulates pluripotency entry and exit by directly regulating POU5F1 stability
  • DPF2 decreases monomeric and mono-ubiquitinated POU5F1, assembles poly-ubiquitin chains on POU5F1 mainly through Ub-K48 linkage
  • NACC1 coordinates differentiation by activating POU5F1 and inhibiting both SOX2 and TCF3
  • DPF2, also named ubi-d4/requiem (REQU), interacts with a protein complex containing POU5F1
  • dynamic interplay between POU2F1 and POU2F5, in particular during the critical window immediately after loss of pluripotency when cells make the earliest developmental fate decisions
  • HELLS assists gene repression upon binding to the POU5F1 promoter region
  • cell & other
    REGULATION
    Phosphorylated by ERK2 (several putative ERK phosphorylation sites, and ERK2 phosphorylated these sites)
    Other self regulation of POU5F1 may be mediated via a negative feedback loop in pluripotent cells
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral       gain of function
    differentially up-regulated in germ cells seminomas
    tumoral     --over  
    in carcinoma in situ/gonadoblastoma, seminomas/germinoma/dysgerminoma, and embryonal carcinoma undifferentiated, and in breast cancer
    tumoral fusion      
    wirh EWSR1 in t(6;22)(p21;q12) associated with bone and soft-tissue tumours resulting in a chimaeric molecule fusing the NTD (N-terminal domain) of the EWSR1 to the CTD (C-terminal domain) of POU5F1 embryonic gene
    Susceptibility to psoriasis
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerdigestiveliver
    co-suppression of POU5F1 and BIRC5 is potentially beneficial for HCC treatment
    ANIMAL & CELL MODELS