Oct-25 (XOct-25; Xenbase pou5f3.2.L) is one of three Xenopus laevis POU class V (Pou5f3) transcription factors, the amphibian counterparts of mammalian Oct4; the others are Oct-60 (pou5f3.3) and Oct-91 (pou5f3.1). It is a nuclear octamer (ATGCAAAT)-binding protein with a POU-specific domain and POU homeodomain. Its mRNA is present at low levels maternally and rises sharply at gastrulation in the animal and marginal zones, then declines by the end of neurulation. When bound directly to octamer sites, as in the BMP-responsive Xvent-2B promoter, it activates transcription. In the early embryo it mainly acts as a partner-dependent repressor. It joins complexes with VegT and Tcf3 on Xnr and Siamois promoters, and with FoxH1, Smad2 and WBSCR11 on goosecoid and Mix2. These complexes damp the nuclear response to the maternal VegT, Wnt/beta-catenin and nodal/activin inducers, keeping embryonic cells undifferentiated and timing germ-layer specification. In the ectoderm it limits competence to respond to BMP, favouring neural over epidermal fate and inducing Sox2. Suv4-20h-dependent H4K20me3 must silence it for neural differentiation to proceed. Zygotic Oct-25 and Oct-91 are also expressed at the neural plate border. There they are required, with Oct-25 alone sufficient for rescue, for neural crest formation. Pou5 proteins therefore act as competence factors that the crest inherits from the pluripotent blastula. Mouse Oct4 and chick OCT4 play a similar role in the crest. Pou5 is a vertebrate innovation derived from a pou3-like ancestor, and its crest-promoting activity is specific to the pou5 clade. Lamprey pou5 is expressed in blastula animal-pole cells but not in the neural crest. Even so, lamprey pou5 can promote crest formation when expressed in frog embryos.
Definition: The process by which neural plate border and premigratory neural crest progenitor cells are kept in an undifferentiated, proliferative and multipotent state until neural crest specification.
Justification: GO:0014029 neural crest formation, which these factors currently carry, is proposed for obsoletion (projects/NEURAL_CREST_FORMATION_OBSOLETION.md). Competence factors (Myc, Id3, Hairy2, Pou5f3/Oct25) are required for crest to form, but loss causes progenitor arrest or death rather than a change of fate, and sustained activity blocks differentiation, so neither crest cell differentiation nor fate specification describes their role. GO:0019827 stem cell population maintenance is the parent; the new term says which progenitor population is maintained.
Parent term: stem cell population maintenance
Supporting Evidence:
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000976 transcription cis-regulatory region binding | IDA PMID:15292233 The POU factor Oct-25 regulates the Xvent-2B gene and counte... | ACCEPT | Summary: Oct-25 was identified in a yeast one-hybrid screen as a factor binding the BMP-responsive Xvent-2B promoter, confirmed in vitro and in vivo. Reason: Direct, sequence-dependent binding of Oct-25 to a pol II promoter is the defining activity of this POU-V factor. Supporting Evidence: PMID:15292233 Oct-25, a Xenopus POU domain protein related to mammalian Oct-3/4, binds as an additional factor to the Xvent-2B promoter PMID:15292233 Luciferase reporter gene assay demonstrated that Oct-25 stimulates transcription of the Xvent-2B gene |
| GO:0000976 transcription cis-regulatory region binding | IDA PMID:17541407 POU-V factors antagonize maternal VegT activity and beta-Cat... | ACCEPT | Summary: EMSA with recombinant and embryo-derived Oct-25 on the Xnr1 and Siamois promoters, with specificity shown by mutated sites and morpholino-depleted extracts, and ChIP in embryos. Reason: Full text shows site-specific EMSA plus anti-Oct-25 ChIP in gastrula embryos (reduced by Oct25MO). Strong direct evidence. Supporting Evidence: PMID:17541407 EMSAs demonstrated that bacterially expressed Oct-25 as well as Oct-25 in embryonic protein extracts specifically bound to the DNA fragment that contains the Oct binding site PMID:17541407 In conclusion, both in vitro and in vivo studies support that Oct-25 interacts with Xnr1 and Siamois promoters. |
| GO:0000976 transcription cis-regulatory region binding | IDA PMID:18922797 Oct25 represses transcription of nodal/activin target genes ... | ACCEPT | Summary: Oct25 binds an octamer motif in the goosecoid promoter by EMSA and occupies the Gsc and Mix2 promoters by ChIP (reduced by Oct25MO). Reason: Direct promoter binding shown in vitro and in embryos (full text). Supporting Evidence: PMID:18922797 EMSAs demonstrated strong binding between Oct25 and the first octamer motif PMID:18922797 The inhibitory effect is achieved by forming repression complexes on the promoters of Gsc and Mix2 between Oct25 and the signal transducers of the nodal/activin pathway, WBSCR11, FAST1, and Smad2 |
| GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT node for POU-domain transcription factors placing sequence-specific binding of pol II cis-regulatory regions. Reason: Oct-25 is a POU-V octamer-binding factor with experimentally shown binding at pol II promoters (Xvent-2B, Xnr1, Siamois, Gsc); the IBA is correct and at the right level. Supporting Evidence: PMID:1732736 Sequences encoding three novel octamer binding-proteins were isolated from Xenopus cDNA libraries PMID:17541407 EMSAs demonstrated that bacterially expressed Oct-25 as well as Oct-25 in embryonic protein extracts specifically bound to the DNA fragment that contains the Oct binding site |
| GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding | IEA GO_REF:0000118 | ACCEPT | Summary: TreeGrafter transfer of pol II cis-regulatory sequence-specific DNA binding. Reason: Consistent with the IBA and with direct EMSA/ChIP evidence for octamer binding at pol II promoters. Supporting Evidence: PMID:18922797 EMSAs demonstrated strong binding between Oct25 and the first octamer motif |
| GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT node assigning pol II-specific DNA-binding transcription factor activity to the POU family. Reason: Core MF. Oct-25 binds octamer sites and regulates pol II genes in both directions (activates Xvent-2B, represses Xnr1/Siamois/Gsc/Mix2). Supporting Evidence: PMID:15292233 Luciferase reporter gene assay demonstrated that Oct-25 stimulates transcription of the Xvent-2B gene PMID:18922797 Here we show that Oct25, an Oct4 homologue in Xenopus, antagonizes the activity of nodal/activin signaling by inhibiting the transcription of its target genes, Gsc and Mix2 |
| GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific | IEA GO_REF:0000120 | ACCEPT | Summary: Combined IEA for pol II-specific DNA-binding transcription factor activity. Reason: Same as the IBA; correct core activity. Supporting Evidence: PMID:15292233 Luciferase reporter gene assay demonstrated that Oct-25 stimulates transcription of the Xvent-2B gene |
| GO:0001702 gastrulation with mouth forming second | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: ARBA rule assigning gastrulation with mouth forming second (deuterostome gastrulation). Reason: Oct-25 acts during gastrula stages to time germ-layer specification by antagonizing mesendoderm inducers; gastrulation defects follow from that, so the term is acceptable but secondary to the transcriptional germ-layer role. Supporting Evidence: PMID:16860542 We conclude that Xenopus Oct proteins are required to control the levels of embryonic signaling pathways, thereby ensuring the correct specification of germ layers |
| GO:0001702 gastrulation with mouth forming second | IMP PMID:16860542 Xenopus POU factors of subclass V inhibit activin/nodal sign... | KEEP AS NON CORE | Summary: Overexpression/knockdown of Xenopus POU-V factors perturbs gastrulation (mesendoderm suppression; ectopic endoderm after combined Oct-25 + Oct-60 knockdown). Reason: Abstract-only cache; the knockdown combined Oct-25 and Oct-60 morpholinos (the same rows sit on oct-60, Q91989). The gastrulation phenotype reflects Oct-25's upstream control of inducing signals rather than a role in gastrulation morphogenesis; keep as non-core, deferring to the curator on the experimental detail. Supporting Evidence: PMID:16860542 Loss of Oct-25 and Oct-60 function results in elevated transcription of mesendodermal marker genes and ectopic formation of endoderm in the equatorial region of gastrula stage embryos PMID:16860542 We conclude that Xenopus Oct proteins are required to control the levels of embryonic signaling pathways, thereby ensuring the correct specification of germ layers |
| GO:0001702 gastrulation with mouth forming second | IMP PMID:16860542 Xenopus POU factors of subclass V inhibit activin/nodal sign... | KEEP AS NON CORE | Summary: Same morpholino experiment as the previous row, with the Xenbase morpholino recorded. Reason: As above: indirect consequence of germ-layer mis-specification after Oct-25/Oct-60 depletion. Supporting Evidence: PMID:16860542 Loss of Oct-25 and Oct-60 function results in elevated transcription of mesendodermal marker genes and ectopic formation of endoderm in the equatorial region of gastrula stage embryos |
| GO:0001841 neural tube formation | IMP PMID:16860542 Xenopus POU factors of subclass V inhibit activin/nodal sign... | KEEP AS NON CORE | Summary: Neural tube formation phenotype recorded by Xenbase from the Oct-25/Oct-60 knockdown study. Reason: Abstract-only; the abstract does not describe a neural tube phenotype, so the detail cannot be verified. It is biologically plausible as a downstream consequence of Oct-25 promoting neural fate in the ectoderm (Sox2 induction; reduced neural tissue after XOct-25 knockdown), so it is kept as a non-core, indirect role rather than overruled. Supporting Evidence: PMID:16860542 Within the ectoderm, Oct-25 promotes neural fate by upregulating neuroectodermal genes, such as Xsox2, which prevent differentiation of neural progenitors into neurons PMID:17950579 inhibition of XOct-25 function in the prospective neuroectoderm resulted in expansion of epidermal ectoderm at the expense of neuroectoderm |
| GO:0003677 DNA binding | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro-based DNA binding (homeodomain, POU domain). Reason: Correct but general; more specific octamer/cis-regulatory binding terms are also present. Supporting Evidence: PMID:1732736 Sequences encoding three novel octamer binding-proteins were isolated from Xenopus cDNA libraries |
| GO:0003700 DNA-binding transcription factor activity | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro POU-domain mapping to DNA-binding transcription factor activity. Reason: Correct, parent of the core GO:0000981. Supporting Evidence: PMID:15292233 Luciferase reporter gene assay demonstrated that Oct-25 stimulates transcription of the Xvent-2B gene |
| GO:0005515 protein binding | IPI PMID:15292233 The POU factor Oct-25 regulates the Xvent-2B gene and counte... | MODIFY | Summary: Oct-25 interacts with Xvent-2 (ventx2.2.S, Q9YH70), a homeodomain transcription factor in the BMP-induced Xvent-2B transcription complex. Reason: Generic protein binding is uninformative. The partner is a DNA-binding homeodomain transcription factor, and the interaction is part of Oct-25 joining a promoter-bound transcription complex, so GO:0140297 DNA-binding transcription factor binding is the evidence-backed term (the same term GOA already uses for the VegT/Tcf3/FoxH1 partners). Proposed replacements: DNA-binding transcription factor binding Supporting Evidence: PMID:15292233 Oct-25 interacts in vitro with components of the Xvent-2B transcription complex, like Smad1/4 and Xvent-2 |
| GO:0005515 protein binding | IPI PMID:17541407 POU-V factors antagonize maternal VegT activity and beta-Cat... | MODIFY | Summary: GST pull-down and co-IP show Oct-25 binds the T-box transcription factor VegT (vegt-a), forming repression complexes on VegT target promoters. Reason: Replace generic protein binding with GO:0140297: VegT is a DNA-binding T-box factor and Oct-25 forms a complex with it on the T-box site of the Xnr1 promoter (full text). Proposed replacements: DNA-binding transcription factor binding Supporting Evidence: PMID:17541407 Oct-25, VegT and Tcf3 interact with each other and form repression complexes on promoters of VegT and beta-Catenin target genes PMID:17541407 Co-immunoprecipitations with fusion proteins demonstrated that VegT and Tcf3 precipitated endogenous Oct-25 |
| GO:0005515 protein binding | IPI PMID:17541407 POU-V factors antagonize maternal VegT activity and beta-Cat... | MODIFY | Summary: Oct-25 binds Tcf3 (tcf7l1-b) and forms a ternary complex with Tcf3 and beta-catenin on TCF/LEF sites. Reason: Tcf3 is an HMG-box DNA-binding transcription factor; GO:0140297 captures the informative function (GOA already carries GO:0140297 for the tcf7l1-a interaction from the same paper). Proposed replacements: DNA-binding transcription factor binding Supporting Evidence: PMID:17541407 Oct-25, VegT and Tcf3 interact with each other and form repression complexes on promoters of VegT and beta-Catenin target genes PMID:17541407 Therefore, in the absence of its binding site, Oct-25 serves as a co-repressor for VegT or Tcf3 to regulate transcription of target genes. |
| GO:0005634 nucleus | IC PMID:15292233 The POU factor Oct-25 regulates the Xvent-2B gene and counte... | ACCEPT | Summary: Nuclear location inferred from promoter binding. Reason: A transcription factor binding promoters in vivo acts in the nucleus; ChIP in embryos (PMID:17541407, PMID:18922797) supports this. Supporting Evidence: PMID:15292233 Oct-25, a Xenopus POU domain protein related to mammalian Oct-3/4, binds as an additional factor to the Xvent-2B promoter PMID:17541407 In conclusion, both in vitro and in vivo studies support that Oct-25 interacts with Xnr1 and Siamois promoters. |
| GO:0005634 nucleus | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt subcellular location mapping (nucleus). Reason: Correct; consistent with promoter occupancy. Supporting Evidence: PMID:17541407 In conclusion, both in vitro and in vivo studies support that Oct-25 interacts with Xnr1 and Siamois promoters. |
| GO:0005667 transcription regulator complex | IC PMID:15292233 The POU factor Oct-25 regulates the Xvent-2B gene and counte... | ACCEPT | Summary: Inferred from Oct-25 binding Smad1/4 in the Xvent-2B promoter complex. Reason: Oct-25 assembles into multi-protein transcription complexes on target promoters (activating at Xvent-2B, repressing at Gsc/Mix2/Xnr1/Siamois); the CC term is appropriate. Supporting Evidence: PMID:15292233 Oct-25 interacts in vitro with components of the Xvent-2B transcription complex, like Smad1/4 and Xvent-2 |
| GO:0005667 transcription regulator complex | IC PMID:18922797 Oct25 represses transcription of nodal/activin target genes ... | ACCEPT | Summary: Inferred from Oct25 binding Smad2 in repression complexes on Gsc/Mix2. Reason: Oct-25 assembles into multi-protein transcription complexes on target promoters (activating at Xvent-2B, repressing at Gsc/Mix2/Xnr1/Siamois); the CC term is appropriate. Supporting Evidence: PMID:18922797 The inhibitory effect is achieved by forming repression complexes on the promoters of Gsc and Mix2 between Oct25 and the signal transducers of the nodal/activin pathway, WBSCR11, FAST1, and Smad2 |
| GO:0005667 transcription regulator complex | IEA GO_REF:0000117 | ACCEPT | Summary: ARBA assignment of transcription regulator complex. Reason: Consistent with the experimental complex data. Supporting Evidence: PMID:17541407 Oct-25, VegT and Tcf3 interact with each other and form repression complexes on promoters of VegT and beta-Catenin target genes |
| GO:0005667 transcription regulator complex | IPI PMID:15292233 The POU factor Oct-25 regulates the Xvent-2B gene and counte... | ACCEPT | Summary: Oct-25 in the Xvent-2B promoter complex with Xvent-2. Reason: Supported by the interaction with complex components on the promoter. Supporting Evidence: PMID:15292233 Oct-25 interacts in vitro with components of the Xvent-2B transcription complex, like Smad1/4 and Xvent-2 |
| GO:0005667 transcription regulator complex | IPI PMID:17541407 POU-V factors antagonize maternal VegT activity and beta-Cat... | ACCEPT | Summary: Oct-25 forms a repression complex with Tcf3 (tcf7l1-a) and VegT on Xnr1 and Siamois promoters. Reason: EMSA supershifts and co-IP of a ternary Oct-25/VegT/Tcf3 complex (full text). Supporting Evidence: PMID:17541407 Oct-25, VegT and Tcf3 interact with each other and form repression complexes on promoters of VegT and beta-Catenin target genes PMID:17541407 Co-immunoprecipitations with fusion proteins demonstrated that VegT and Tcf3 precipitated endogenous Oct-25 |
| GO:0005667 transcription regulator complex | IPI PMID:17541407 POU-V factors antagonize maternal VegT activity and beta-Cat... | ACCEPT | Summary: Oct-25 forms a repression complex with VegT on the Xnr1 promoter. Reason: As above. Supporting Evidence: PMID:17541407 Oct-25, VegT and Tcf3 interact with each other and form repression complexes on promoters of VegT and beta-Catenin target genes |
| GO:0005667 transcription regulator complex | IPI PMID:18922797 Oct25 represses transcription of nodal/activin target genes ... | ACCEPT | Summary: Oct25 forms a repression complex with WBSCR11 (Gtf2ird1) on the goosecoid distal element. Reason: EMSA supershift and co-IP (full text). Supporting Evidence: PMID:18922797 The inhibitory effect is achieved by forming repression complexes on the promoters of Gsc and Mix2 between Oct25 and the signal transducers of the nodal/activin pathway, WBSCR11, FAST1, and Smad2 PMID:18922797 In co-transfected cells, an anti-HA antibody could precipitate the immunocomplex comprising N-terminally Flag-tagged Oct25 and C-terminally HA-tagged Smad2, XWBSCR11 or FAST1 |
| GO:0006355 regulation of DNA-templated transcription | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro mapping to regulation of DNA-templated transcription. Reason: Correct general process for a POU transcription factor. Supporting Evidence: PMID:15292233 Luciferase reporter gene assay demonstrated that Oct-25 stimulates transcription of the Xvent-2B gene |
| GO:0006357 regulation of transcription by RNA polymerase II | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT assignment of regulation of transcription by RNA polymerase II to the POU family. Reason: Correct; Oct-25 activates and represses pol II genes. Supporting Evidence: PMID:15292233 Luciferase reporter gene assay demonstrated that Oct-25 stimulates transcription of the Xvent-2B gene PMID:18922797 Here we show that Oct25, an Oct4 homologue in Xenopus, antagonizes the activity of nodal/activin signaling by inhibiting the transcription of its target genes, Gsc and Mix2 |
| GO:0006357 regulation of transcription by RNA polymerase II | IEA GO_REF:0000118 | ACCEPT | Summary: TreeGrafter transfer of regulation of transcription by RNA polymerase II. Reason: Correct, consistent with the IBA. Supporting Evidence: PMID:18922797 Here we show that Oct25, an Oct4 homologue in Xenopus, antagonizes the activity of nodal/activin signaling by inhibiting the transcription of its target genes, Gsc and Mix2 |
| GO:0007369 gastrulation | IMP PMID:16860542 Xenopus POU factors of subclass V inhibit activin/nodal sign... | KEEP AS NON CORE | Summary: Gastrulation annotation from the POU-V knockdown/overexpression study. Reason: Oct-25's role is upstream: it times germ-layer specification by restraining inducing signals. Gastrulation defects are a consequence; keep as non-core (abstract-only cache, combined Oct-25/Oct-60 knockdown). Supporting Evidence: PMID:16860542 Loss of Oct-25 and Oct-60 function results in elevated transcription of mesendodermal marker genes and ectopic formation of endoderm in the equatorial region of gastrula stage embryos PMID:16860542 We conclude that Xenopus Oct proteins are required to control the levels of embryonic signaling pathways, thereby ensuring the correct specification of germ layers |
| GO:0009948 anterior/posterior axis specification | IMP PMID:16860542 Xenopus POU factors of subclass V inhibit activin/nodal sign... | MARK AS OVER ANNOTATED | Summary: Anterior/posterior axis specification recorded by Xenbase from the combined Oct-25/Oct-60 morpholino experiment. Reason: Not wrong as an upstream phenotype, but Oct-25 does not specify the A/P axis. The axis defects (and A/P truncations after overexpression, PMID:15292233) are downstream of mis-timed germ-layer specification. The abstract describes no axis-specification role, and the same rows also sit on oct-60 (Q91989). This is a phenotype transcription rather than a function; not removed because the full text is not available. Supporting Evidence: PMID:16860542 Loss of Oct-25 and Oct-60 function results in elevated transcription of mesendodermal marker genes and ectopic formation of endoderm in the equatorial region of gastrula stage embryos PMID:15292233 Overexpression of Oct-25 results in anterior/posterior truncations and lack of differentiation for neuroectoderm- and mesoderm-derived tissues including blood cells |
| GO:0030514 negative regulation of BMP signaling pathway | IMP PMID:17950579 The Xenopus POU class V transcription factor XOct-25 inhibit... | ACCEPT | Summary: XOct-25 limits the competence of ectoderm to respond to BMP downstream of receptor activation; morphant ectoderm is hypersensitive to BMP and the neural loss is rescued by reducing BMP signalling. Reason: Core role in ectodermal patterning, consistent with Oct-25 joining BMP-responsive Smad complexes (Xvent-2B). Abstract-only, but the abstract states both GOF and LOF with BMP rescue. Supporting Evidence: PMID:17950579 XOct-25 suppressed early BMP responses of ectodermal cells downstream of BMP receptor activation and promoted neural induction while suppressing epidermal differentiation PMID:17950579 inhibition of XOct-25 function in the prospective neuroectoderm resulted in expansion of epidermal ectoderm at the expense of neuroectoderm |
| GO:0032926 negative regulation of activin receptor signaling pathway | IMP PMID:16860542 Xenopus POU factors of subclass V inhibit activin/nodal sign... | ACCEPT | Summary: Oct-25 (with Oct-60) inhibits activin/nodal signalling; loss of function elevates mesendodermal genes. Reason: Core role, independently confirmed mechanistically in PMID:18922797 (repression complexes with Smad2/FoxH1/WBSCR11 on Gsc/Mix2). Note LOF combined Oct-25 and Oct-60. Supporting Evidence: PMID:16860542 Oct-25 and Oct-60 are shown to inhibit activin/nodal and FGF signaling pathways PMID:16860542 Loss of Oct-25 and Oct-60 function results in elevated transcription of mesendodermal marker genes and ectopic formation of endoderm in the equatorial region of gastrula stage embryos file:XENLA/pou5f1.1/pou5f1.1-deep-research-falcon.md Oct-25 controls how embryonic cells transcribe responses to germ-layer-inducing signals |
| GO:0032926 negative regulation of activin receptor signaling pathway | IMP PMID:18922797 Oct25 represses transcription of nodal/activin target genes ... | ACCEPT | Summary: Oct25 knockdown enhances and overexpression suppresses nodal/activin target genes Gsc and Mix2, including in Xnr1-injected animal caps. Reason: Core role with direct mechanism (nuclear repression complexes with the pathway transducers). Oct25-specific morpholino. Supporting Evidence: PMID:18922797 Here we show that Oct25, an Oct4 homologue in Xenopus, antagonizes the activity of nodal/activin signaling by inhibiting the transcription of its target genes, Gsc and Mix2 PMID:18922797 The inhibitory effect is achieved by forming repression complexes on the promoters of Gsc and Mix2 between Oct25 and the signal transducers of the nodal/activin pathway, WBSCR11, FAST1, and Smad2 |
| GO:0036342 post-anal tail morphogenesis | IMP PMID:16860542 Xenopus POU factors of subclass V inhibit activin/nodal sign... | MARK AS OVER ANNOTATED | Summary: Post-anal tail morphogenesis phenotype from the combined Oct-25/Oct-60 knockdown. Reason: Tail defects are a late, indirect consequence of early germ-layer mis-specification; Oct-25 expression has declined by the end of neurulation. Not a function of the protein. Not removed because the full text is not available. Supporting Evidence: PMID:16860542 Loss of Oct-25 and Oct-60 function results in elevated transcription of mesendodermal marker genes and ectopic formation of endoderm in the equatorial region of gastrula stage embryos PMID:1732736 Transcripts from a second POU-domain gene, Oct-25, were present at low levels in oocytes and early embryos and were dramatically upregulated during early gastrulation |
| GO:0043565 sequence-specific DNA binding | IDA PMID:1732736 Sequential expression of multiple POU proteins during amphib... | ACCEPT | Summary: Oct-25 was cloned as an octamer-binding POU protein from Xenopus cDNA libraries. Reason: Octamer (ATGCAAAT) binding is the defining POU activity, confirmed by later EMSAs. Supporting Evidence: PMID:1732736 Sequences encoding three novel octamer binding-proteins were isolated from Xenopus cDNA libraries |
| GO:0043565 sequence-specific DNA binding | IEA GO_REF:0000117 | ACCEPT | Summary: ARBA assignment of sequence-specific DNA binding. Reason: Correct. Supporting Evidence: PMID:18922797 EMSAs demonstrated strong binding between Oct25 and the first octamer motif |
| GO:0045605 negative regulation of epidermal cell differentiation | IMP PMID:17950579 The Xenopus POU class V transcription factor XOct-25 inhibit... | ACCEPT | Summary: XOct-25 suppresses epidermal differentiation; knockdown expands epidermal ectoderm at the expense of neuroectoderm. Reason: Directly stated GOF and LOF result; part of Oct-25's core role in controlling ectodermal fate choice by limiting BMP responsiveness. Supporting Evidence: PMID:17950579 XOct-25 suppressed early BMP responses of ectodermal cells downstream of BMP receptor activation and promoted neural induction while suppressing epidermal differentiation PMID:17950579 inhibition of XOct-25 function in the prospective neuroectoderm resulted in expansion of epidermal ectoderm at the expense of neuroectoderm |
| GO:0045892 negative regulation of DNA-templated transcription | IMP PMID:17541407 POU-V factors antagonize maternal VegT activity and beta-Cat... | MODIFY | Summary: Oct-25/Oct-60 depletion elevates, and Oct-25 overexpression represses, VegT and beta-catenin target genes (Xnr1-6, Siamois) and their promoter reporters. Reason: Correct but more precise term available: the targets (Xnrs, Siamois) are pol II genes repressed through promoter complexes, so GO:0000122 negative regulation of transcription by RNA polymerase II. Proposed replacements: negative regulation of transcription by RNA polymerase II Supporting Evidence: PMID:17541407 Oct-25, VegT and Tcf3 interact with each other and form repression complexes on promoters of VegT and beta-Catenin target genes PMID:17541407 functional knockdown of Oct-25 and Oct-60 by injection of a mixture of characterized antisense morpholino oligos against Oct-25 (Oct25MOs) and Oct-60 (Oct60MOs) |
| GO:0045892 negative regulation of DNA-templated transcription | IMP PMID:18922797 Oct25 represses transcription of nodal/activin target genes ... | MODIFY | Summary: Oct25 represses Gsc and Mix2 transcription; knockdown up-regulates them. Reason: Refine to GO:0000122: the repressed genes are pol II-transcribed promoters occupied by Oct25 (ChIP). Proposed replacements: negative regulation of transcription by RNA polymerase II Supporting Evidence: PMID:18922797 Here we show that Oct25, an Oct4 homologue in Xenopus, antagonizes the activity of nodal/activin signaling by inhibiting the transcription of its target genes, Gsc and Mix2 PMID:18922797 The inhibitory effect is achieved by forming repression complexes on the promoters of Gsc and Mix2 between Oct25 and the signal transducers of the nodal/activin pathway, WBSCR11, FAST1, and Smad2 |
| GO:0045893 positive regulation of DNA-templated transcription | IDA PMID:15292233 The POU factor Oct-25 regulates the Xvent-2B gene and counte... | ACCEPT | Summary: Oct-25 stimulates the Xvent-2B promoter, dependent on its binding site and the BMP-responsive element. Reason: Direct reporter evidence of activation when bound to its site. Supporting Evidence: PMID:15292233 Luciferase reporter gene assay demonstrated that Oct-25 stimulates transcription of the Xvent-2B gene |
| GO:0045893 positive regulation of DNA-templated transcription | IDA PMID:17950579 The Xenopus POU class V transcription factor XOct-25 inhibit... | ACCEPT | Summary: Positive transcription regulation from the XOct-25 ectodermal competence study (abstract-only). Reason: The abstract does not detail the assay, but Oct-25 activation of neuroectodermal genes (e.g. Sox2) is documented independently (PMID:16860542); deferring to the curator. Supporting Evidence: PMID:17950579 XOct-25 suppressed early BMP responses of ectodermal cells downstream of BMP receptor activation and promoted neural induction while suppressing epidermal differentiation PMID:16860542 Within the ectoderm, Oct-25 promotes neural fate by upregulating neuroectodermal genes, such as Xsox2, which prevent differentiation of neural progenitors into neurons |
| GO:0045893 positive regulation of DNA-templated transcription | IDA PMID:18922797 Oct25 represses transcription of nodal/activin target genes ... | ACCEPT | Summary: Wild-type Oct25 mildly stimulates an octamer-repeat reporter (OctLuc8x). Reason: Shows intrinsic activator capacity when bound directly to octamer sites; physiologically Oct25 is bifunctional (activator on its own sites, co-repressor in partner complexes). Supporting Evidence: PMID:18922797 OctLuc8x was mildly stimulated by wild-type Oct25 but strongly stimulated by VP16-Oct25 |
| GO:0046332 SMAD binding | IDA PMID:15292233 The POU factor Oct-25 regulates the Xvent-2B gene and counte... | ACCEPT | Summary: Oct-25 binds Smad1 and Smad4 of the BMP-responsive Xvent-2B complex in vitro. Reason: SMAD binding is informative: it is how Oct-25 engages the BMP and nodal transcriptional responses. Supporting Evidence: PMID:15292233 Oct-25 interacts in vitro with components of the Xvent-2B transcription complex, like Smad1/4 and Xvent-2 |
| GO:0046332 SMAD binding | IDA PMID:18922797 Oct25 represses transcription of nodal/activin target genes ... | ACCEPT | Summary: Oct25 binds Smad2 by GST pull-down and co-IP. Reason: Mechanistic basis of its repression of nodal/activin target genes. Supporting Evidence: PMID:18922797 In co-transfected cells, an anti-HA antibody could precipitate the immunocomplex comprising N-terminally Flag-tagged Oct25 and C-terminally HA-tagged Smad2, XWBSCR11 or FAST1 PMID:18922797 The inhibitory effect is achieved by forming repression complexes on the promoters of Gsc and Mix2 between Oct25 and the signal transducers of the nodal/activin pathway, WBSCR11, FAST1, and Smad2 |
| GO:0050767 regulation of neurogenesis | IMP PMID:17950579 The Xenopus POU class V transcription factor XOct-25 inhibit... | KEEP AS NON CORE | Summary: Regulation of neurogenesis annotation from the XOct-25 ectodermal fate study. Reason: Oct-25 promotes neural (vs epidermal) fate and keeps neural progenitors undifferentiated (Sox2), and must later be silenced for neural differentiation (PMID:23382689). Regulation of neurogenesis is a fair, but broad and secondary, description of these effects. Supporting Evidence: PMID:17950579 These results document an essential role for XOct-25 in commitment to neural or epidermal cell fates in the ectoderm PMID:23382689 Since knockdown of Oct-25 protein significantly rescues the neural differentiation defect in xSuv4-20h double-morphant embryos |
| GO:0060322 head development | IMP PMID:16860542 Xenopus POU factors of subclass V inhibit activin/nodal sign... | KEEP AS NON CORE | Summary: Head development phenotype recorded by Xenbase from the combined Oct-25/Oct-60 knockdown. Reason: Indirect; plausibly reflects reduced neural/anterior tissue after loss of Oct-25's neural-promoting and germ-layer timing functions. Kept as non-core rather than overruled (abstract-only cache). Supporting Evidence: PMID:16860542 Within the ectoderm, Oct-25 promotes neural fate by upregulating neuroectodermal genes, such as Xsox2, which prevent differentiation of neural progenitors into neurons PMID:16860542 Loss of Oct-25 and Oct-60 function results in elevated transcription of mesendodermal marker genes and ectopic formation of endoderm in the equatorial region of gastrula stage embryos |
| GO:0090575 RNA polymerase II transcription regulator complex | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT assignment of RNA polymerase II transcription regulator complex. Reason: Oct-25 forms promoter-bound complexes with Smads, FoxH1, WBSCR11, VegT and Tcf3 at pol II genes; this is the precise CC. Supporting Evidence: PMID:18922797 The inhibitory effect is achieved by forming repression complexes on the promoters of Gsc and Mix2 between Oct25 and the signal transducers of the nodal/activin pathway, WBSCR11, FAST1, and Smad2 PMID:17541407 Oct-25, VegT and Tcf3 interact with each other and form repression complexes on promoters of VegT and beta-Catenin target genes |
| GO:0140297 DNA-binding transcription factor binding | IEA GO_REF:0000117 | ACCEPT | Summary: ARBA assignment of DNA-binding transcription factor binding. Reason: Consistent with the IPI evidence for VegT, Tcf3, FoxH1 and Vent2. Supporting Evidence: PMID:17541407 Oct-25, VegT and Tcf3 interact with each other and form repression complexes on promoters of VegT and beta-Catenin target genes |
| GO:0140297 DNA-binding transcription factor binding | IPI PMID:17541407 POU-V factors antagonize maternal VegT activity and beta-Cat... | ACCEPT | Summary: Oct-25 binds Tcf3 (tcf7l1-a). Reason: Informative MF: the interaction converts the beta-catenin/Tcf3 activation complex into a repressive one. Supporting Evidence: PMID:17541407 Oct-25, VegT and Tcf3 interact with each other and form repression complexes on promoters of VegT and beta-Catenin target genes PMID:17541407 Therefore, in the absence of its binding site, Oct-25 serves as a co-repressor for VegT or Tcf3 to regulate transcription of target genes. |
| GO:0140297 DNA-binding transcription factor binding | IPI PMID:18922797 Oct25 represses transcription of nodal/activin target genes ... | ACCEPT | Summary: Oct25 binds WBSCR11 (Gtf2ird1), a DNA-binding factor on the Gsc distal element. Reason: Pull-down and co-IP; WBSCR11 binds the Gsc DE. Supporting Evidence: PMID:18922797 In co-transfected cells, an anti-HA antibody could precipitate the immunocomplex comprising N-terminally Flag-tagged Oct25 and C-terminally HA-tagged Smad2, XWBSCR11 or FAST1 |
| GO:0140297 DNA-binding transcription factor binding | IPI PMID:18922797 Oct25 represses transcription of nodal/activin target genes ... | ACCEPT | Summary: Oct25 binds FAST1/FoxH1 (the GOA WITH entry is human FOXH1, O75593). Reason: Interaction with the forkhead DNA-binding transducer of nodal signalling; the partner identifier is the human protein, but the paper describes Xenopus FAST1 constructs (curator choice, not changed). Supporting Evidence: PMID:18922797 In co-transfected cells, an anti-HA antibody could precipitate the immunocomplex comprising N-terminally Flag-tagged Oct25 and C-terminally HA-tagged Smad2, XWBSCR11 or FAST1 PMID:18922797 The inhibitory effect is achieved by forming repression complexes on the promoters of Gsc and Mix2 between Oct25 and the signal transducers of the nodal/activin pathway, WBSCR11, FAST1, and Smad2 |
| NTR neural crest progenitor maintenance | IMP PMID:39060477 Shared features of blastula and neural crest stem cells evol... | NEW | Summary: Zygotic Oct25 (pou5f3.2) and Oct91 (pou5f3.1) are expressed at the neural plate border and in early crest. Depleting both (L and S morpholinos) nearly abolishes snai2 and foxd3 and reduces pax3. Oct25 alone rescues, and Oct25 gain of function expands border and crest markers. Reason: Synthesis: (1) expression in border/crest cells; (2) a DNA-binding transcription factor whose POU5 orthologs (OCT4) bind neural crest enhancers with TFAP2A in chick/human (PMID:36182685) and are required for cranial crest ectomesenchyme in mouse (PMID:33542111); (3) LOF with paralog-specific rescue by this protein; (4) GOF expands border and crest. Layer: competence factor carried from the blastula, not a specifier. It is broadly ectodermal, it also promotes neural fate (sox3 expansion), and LOF lowers the border marker pax3 as well as crest specifiers. It therefore takes the proposed term neural crest progenitor maintenance (NTR), not GO:0014036; GO:0014029 is proposed for obsoletion (projects/NEURAL_CREST_FORMATION_OBSOLETION.md). Participation: it is a transcription factor acting in the forming crest cells, not a substrate. Comparator check (QuickGO 2026-10-07, queries in notes): no POU5 protein in human, mouse, rat, zebrafish, chicken or either Xenopus carries any neural crest term. The POU5 crest papers (2021-2024) are uncurated, while same-layer potency peers carry crest terms (id3-a crest IMP rows; zebrafish mych GO:0014032 IMP; foxd3, snai1). So this is curation lag, not a convention. Caveat: the LOF hit pou5f3.1 and pou5f3.2 together. Supporting Evidence: PMID:39060477 zygotic pou5f3.1 and pou5f3.2 expressed in the neural plate border and neural crest PMID:39060477 pou5f3 depletion resulted in a near-total loss of snai2 and foxd3 neural crest expression PMID:39060477 We found that lamprey and Xenopus pou5 orthologs were indistinguishable in their ability to restore snai2 and foxd3 expression PMID:39060477 All pou5 factors were found to expand the expression domain of neural plate border and neural crest markers pax3, zic1, and snai2 to comparable extents PMID:39060477 we hypothesize that pou5 activity helps maintain a similar progenitor state in the neural crest PMID:36182685 Binding of OCT4-SOX2 to neural crest enhancers requires pioneer factor TFAP2A PMID:33542111 Pluripotency factor Oct4 is transiently reactivated in CNCCs and is required for the subsequent formation of ectomesenchyme |
| GO:0003714 transcription corepressor activity | IDA PMID:17541407 POU-V factors antagonize maternal VegT activity and beta-Cat... | NEW | Summary: Oct-25 represses VegT- and beta-catenin/Tcf3-activated Xnr1 and Siamois promoters even when its own octamer site is mutated, by joining VegT and Tcf3 complexes on their sites. The same protein-interaction mode represses Gsc and Mix2 through FoxH1/Smad2/WBSCR11. Reason: Reporter assays with site mutants (full text) show repression that does not need Oct-25's own DNA binding and depends on partner transcription factors, which defines corepressor activity. The authors state this function explicitly, and PMID:18922797 shows the same mode for nodal targets (VP16- and EVE-fusions both repress). This is the most informative description of how Oct-25 restrains inducing signals. It complements, rather than replaces, its sequence-specific activator activity on octamer sites. Supporting Evidence: PMID:17541407 Therefore, in the absence of its binding site, Oct-25 serves as a co-repressor for VegT or Tcf3 to regulate transcription of target genes. PMID:18922797 The inhibitory effect is achieved by forming repression complexes on the promoters of Gsc and Mix2 between Oct25 and the signal transducers of the nodal/activin pathway, WBSCR11, FAST1, and Smad2 |
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Download this section (compressed HTML)Q: Should GO:0019827 stem cell population maintenance (or a new 'maintenance of embryonic/progenitor competence' term) apply to Xenopus Oct-25? Frog evidence shows timing of germ-layer specification and of ectodermal fate choice. It does not show maintenance of a self-renewing stem cell population, so GO:0019827 (carried by mouse Pou5f1 for ICM/ES self-renewal) was not added. This bears on the module's open competence-maintenance knowledge gap.
Q: York 2024 places zygotic pou5f3.2 at the neural plate border and in early crest. Nicetto 2013 describes Oct-25 restricted to the notoplate by midneurula. Which cells express Oct-25 protein at stages 13-17, and is the border expression Oct-25, Oct-91, or both?
Q: Does frog Oct-25 occupy neural crest enhancers directly, with Sox2/3 and TFAP2A, as OCT4-SOX2 does in chick and human crest (PMID:36182685)? Or does it act at the border indirectly, through its ectodermal anti-BMP and anti-differentiation activities?
Q: Should the neural crest formation annotation be shared with Oct-91 (B7ZQA9) and the S homeolog? The morpholinos hit pou5f3.1 and pou5f3.2 (L and S), and either paralog rescues.
Q: Nomenclature: UniProt names Q7T103 pou5f1.1, whereas Xenbase, RefSeq-linked literature and York 2024 use pou5f3.2. Should UniProt adopt the Pou5f3 nomenclature to avoid paralog confusion?
Experiment: Paralog-specific CRISPR F0 knockouts of pou5f3.2 vs pou5f3.1 (both homeologs), scoring pax3, snai2, foxd3 and sox10 at the border. This would test whether Oct-25 alone is required for crest formation, separately from its gastrula germ-layer role (for example by using stage-restricted, hormone-inducible dominant-negative constructs).
Experiment: CUT&RUN for Oct-25 in neural plate border explants (Pax3/Zic1- or Wnt/chordin-induced animal caps) compared with blastula caps, to test reuse versus retargeting of Oct-25 binding sites and co-occupancy with Sox3 and Tfap2a.
Experiment: Swap the Oct-25 C-terminal domain and the pou3-distinguishing linker residues (MAPK and SUMO sites) into Pou3 and back. This would map the residues responsible for pou5-specific crest-promoting activity.
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