Snai1 (Snail1, Xsna) is a Snail-family C2H2 zinc-finger transcriptional repressor of Xenopus laevis (this entry is the L homeolog). An N-terminal SNAG motif recruits corepressors, including the Ajuba-family LIM proteins Ajuba, LIMD1 and WTIP, and five C-terminal zinc fingers recognise E-box elements in RNA polymerase II promoters; the protein is labile and is stabilised by Elp3, which binds the zinc-finger region and limits beta-Trcp-mediated ubiquitination. snai1 has maternal vegetal transcripts and is expressed zygotically from stage 9 in the dorsal marginal zone and then in all early involuting mesoderm, where it is induced by mesoderm-inducing signals and later down-regulated as mesodermal tissues differentiate. It is also co-expressed with Oct/Sox/Vent pluripotency factors in blastula animal-pole cells and is required there to maintain that network and the competence of these cells to respond to mesoderm- and endoderm-inducing signals. From stage 11 snai1 is switched on in the ectoderm surrounding the prospective neural plate, among the first genes activated in crest progenitors by the border factors Pax3 and Zic1 (Zic1 binds an upstream snai1 element directly), and before snai2. Snail1 specifies neural crest fate: it is sufficient to induce Slug, FoxD3, Twist, Zic5 and Ets1 in naive ectoderm without neural plate or mesoderm markers, is required for crest specification upstream of Slug, and later contributes to crest migration, persisting in migrating crest and some derivatives. Snail border expression is ancestral in chordates (amphioxus Snail is transiently expressed at the neural plate border), and lamprey has a single snail gene expressed in both blastula and crest; after the gnathostome duplication the frog Snai1 paralog retained the blastula and earliest crest roles, while Snai2 took on the definitive crest-specifier and EMT dynamics.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000122 negative regulation of transcription by RNA polymerase II | IDA PMID:12490555 Snail precedes slug in the genetic cascade required for the ... | ACCEPT | Summary: Negative regulation of RNA polymerase II transcription, from Aybar et al. 2003 (repressor-domain fusions of the Xsnail zinc fingers). Reason: An Engrailed-repressor fusion of the Xsnail zinc-finger region mimics Snail gain of function in the crest while an E1A-activator fusion antagonises it, showing that Snail works by sequence-specific repression; Snail also represses Delta1 at the crest border. Snail-family repression of Pol II promoters through SNAG-recruited corepressors is conserved. Direct frog target promoters have not been mapped (no frog ChIP), but the process term is well supported. Core. Supporting Evidence: PMID:12490555 We show that Snail is required for neural crest specification and migration and that it works as a transcriptional repressor. file:XENLA/snai1/snai1-deep-research-falcon.md a fusion of the Xsnail zinc-finger region to an Engrailed repression domain expanded neural-crest-marker expression, whereas fusion to an E1A activation domain inhibited those markers PMID:14681193 At the early gastrula stage, the coordinated action of Xiro1, as a positive regulator, and Snail, as a repressor, restricts the expression of Delta 1 at the border of the neural crest territory. |
| GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding | IBA GO_REF:0000033 | ACCEPT | Summary: IBA (PTN002810938, Snail/Slug/Scratch clade): RNA polymerase II cis-regulatory region sequence-specific DNA binding. Reason: The five C2H2 zinc fingers are the conserved E-box-binding domain of the Snail family; the target lies inside the clade in which E-box binding was established experimentally (human/mouse SNAI1, SNAI2). Frog-specific binding has been shown only indirectly (the zinc-finger region confers target specificity to repressor/activator fusions). Correct and core. Supporting Evidence: file:XENLA/snai1/snai1-uniprot.txt Belongs to the snail C2H2-type zinc-finger protein family. file:XENLA/snai1/snai1-deep-research-falcon.md a fusion of the Xsnail zinc-finger region to an Engrailed repression domain expanded neural-crest-marker expression, whereas fusion to an E1A activation domain inhibited those markers |
| GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding | IEA GO_REF:0000118 | ACCEPT | Summary: TreeGrafter IEA for the same Pol II cis-regulatory sequence-specific DNA binding. Reason: Same assertion as the IBA row; correct for a Snail-family zinc-finger repressor. Supporting Evidence: file:XENLA/snai1/snai1-uniprot.txt Belongs to the snail C2H2-type zinc-finger protein family. |
| GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific | IBA GO_REF:0000033 | ACCEPT | Summary: IBA: DNA-binding transcription factor activity, RNA polymerase II-specific. Reason: Correct for the clade and for frog Snail1. The activity is more precisely repression (repressor-fusion mimicry), so the child term GO:0001227 is added as NEW rather than modifying the phylogenetic annotation, as was done for snai2. Supporting Evidence: PMID:12490555 We show that Snail is required for neural crest specification and migration and that it works as a transcriptional repressor. file:XENLA/snai1/snai1-deep-research-falcon.md a fusion of the Xsnail zinc-finger region to an Engrailed repression domain expanded neural-crest-marker expression, whereas fusion to an E1A activation domain inhibited those markers |
| GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific | IEA GO_REF:0000118 | ACCEPT | Summary: TreeGrafter IEA: DNA-binding transcription factor activity, RNA polymerase II-specific. Reason: Correct, if general; repressor activity is captured by the NEW GO:0001227 row. Supporting Evidence: PMID:12490555 We show that Snail is required for neural crest specification and migration and that it works as a transcriptional repressor. |
| GO:0001755 neural crest cell migration | IEA GO_REF:0000117 | ACCEPT | Summary: ARBA machine-learning IEA for neural crest cell migration. Reason: Consistent with the frog experimental evidence (see IMP row). Supporting Evidence: PMID:12490555 We show that Snail is required for neural crest specification and migration and that it works as a transcriptional repressor. file:XENLA/snai1/snai1-deep-research-falcon.md When Xsnail was activated **after crest specification**, the Slug-positive migrating population increased in **81% of embryos (n=43)**; a dominant-negative Xsnail construct reduced migration in **67% (n=48)**. |
| GO:0001755 neural crest cell migration | IMP PMID:12490555 Snail precedes slug in the genetic cascade required for the ... | ACCEPT | Summary: Neural crest cell migration from Aybar et al. 2003: inducible dominant-negative Snail after specification reduces crest migration; activated Snail expands the migrating population. Reason: Xsnail stays on in migrating crest; stage-controlled (post-specification) inhibition reduces migration and activation expands the migrating Slug-positive population; Elp3 morphant migration defects are rescued by Snail1 and depend on Snail1 protein stability. As a repressor of epithelial programmes Snail1 does part of the work of crest emigration. Core (the later, EMT-effector face of Snail1), shared with snai2. Supporting Evidence: PMID:12490555 We show that Snail is required for neural crest specification and migration and that it works as a transcriptional repressor. file:XENLA/snai1/snai1-deep-research-falcon.md When Xsnail was activated **after crest specification**, the Slug-positive migrating population increased in **81% of embryos (n=43)**; a dominant-negative Xsnail construct reduced migration in **67% (n=48)**. PMID:8305705 Xsna expression persists in the neural crest during migration and in some derivatives at least until metamorphosis PMID:27189455 co-injection of mouse Snail1 (mSnail1) mRNA restored the migration of neural crest cells in the Elp3 morphants |
| GO:0005515 protein binding | IPI PMID:18331720 Ajuba LIM proteins are snail/slug corepressors required for ... | MODIFY | Summary: IPI with Xenopus limd1 (Q06BR1), an Ajuba-family LIM protein, from Langer et al. 2008. Reason: Generic protein binding is uninformative. The Ajuba-family LIM proteins (Ajuba, LIMD1, WTIP) bind the SNAG repression domain and act as functional corepressors of Snail, contributing to Snail-dependent repression and required for Snail/Slug function in Xenopus crest. The informative function is transcription corepressor binding (GO:0001222), the same replacement used for snai2. Proposed replacements: transcription corepressor binding Supporting Evidence: PMID:18331720 Here, we identify the Ajuba family of LIM proteins as functional corepressors of the Snail family via an interaction with the SNAG domain. PMID:18331720 Ajuba LIM proteins contribute to neural crest development as Snail/Slug corepressors and are required for in vivo Snail/Slug function |
| GO:0005515 protein binding | IPI PMID:18331720 Ajuba LIM proteins are snail/slug corepressors required for ... | MODIFY | Summary: IPI with mouse Wtip (Q7TQJ8), an Ajuba-family LIM protein, from Langer et al. 2008. Reason: Generic protein binding is uninformative. The Ajuba-family LIM proteins (Ajuba, LIMD1, WTIP) bind the SNAG repression domain and act as functional corepressors of Snail, contributing to Snail-dependent repression and required for Snail/Slug function in Xenopus crest. The informative function is transcription corepressor binding (GO:0001222), the same replacement used for snai2. Proposed replacements: transcription corepressor binding Supporting Evidence: PMID:18331720 Here, we identify the Ajuba family of LIM proteins as functional corepressors of the Snail family via an interaction with the SNAG domain. PMID:18331720 Ajuba LIM proteins contribute to neural crest development as Snail/Slug corepressors and are required for in vivo Snail/Slug function |
| GO:0005515 protein binding | IPI PMID:18331720 Ajuba LIM proteins are snail/slug corepressors required for ... | MODIFY | Summary: IPI with mouse Ajuba (Q91XC0), an Ajuba-family LIM protein, from Langer et al. 2008. Reason: Generic protein binding is uninformative. The Ajuba-family LIM proteins (Ajuba, LIMD1, WTIP) bind the SNAG repression domain and act as functional corepressors of Snail, contributing to Snail-dependent repression and required for Snail/Slug function in Xenopus crest. The informative function is transcription corepressor binding (GO:0001222), the same replacement used for snai2. Proposed replacements: transcription corepressor binding Supporting Evidence: PMID:18331720 Here, we identify the Ajuba family of LIM proteins as functional corepressors of the Snail family via an interaction with the SNAG domain. PMID:18331720 Ajuba LIM proteins contribute to neural crest development as Snail/Slug corepressors and are required for in vivo Snail/Slug function |
| GO:0005515 protein binding | IPI PMID:18331720 Ajuba LIM proteins are snail/slug corepressors required for ... | MODIFY | Summary: IPI with mouse Limd1 (Q9QXD8), an Ajuba-family LIM protein, from Langer et al. 2008. Reason: Generic protein binding is uninformative. The Ajuba-family LIM proteins (Ajuba, LIMD1, WTIP) bind the SNAG repression domain and act as functional corepressors of Snail, contributing to Snail-dependent repression and required for Snail/Slug function in Xenopus crest. The informative function is transcription corepressor binding (GO:0001222), the same replacement used for snai2. Proposed replacements: transcription corepressor binding Supporting Evidence: PMID:18331720 Here, we identify the Ajuba family of LIM proteins as functional corepressors of the Snail family via an interaction with the SNAG domain. PMID:18331720 Ajuba LIM proteins contribute to neural crest development as Snail/Slug corepressors and are required for in vivo Snail/Slug function |
| GO:0005515 protein binding | IPI PMID:27189455 Elongator Protein 3 (Elp3) stabilizes Snail1 and regulates n... | REMOVE | Summary: IPI with Elp3 (Q5HZM6): Elp3 binds the Snail1 zinc-finger region and inhibits beta-Trcp-mediated ubiquitination, stabilising Snail1. Reason: Generic protein binding is uninformative. Elp3 is an upstream regulator of Snail1 protein stability, not a corepressor or partner through which Snail1 executes its function, so no more specific Snail1 molecular function follows. Removal does not dispute the interaction (consistent with the snai2 Elp3 row). Supporting Evidence: PMID:27189455 Unexpectedly, the zinc finger domain, not the SNAG domain of Snail1, is indispensable for the interaction PMID:27189455 Thus, we favor the model that Elp3 binds and stabilizes Snail1, which is required for the transactivation of mesenchymal genes. |
| GO:0005634 nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: IBA: nucleus (is_active_in). Reason: Snail1 acts as a DNA-binding transcriptional repressor; Ajuba LIM corepressors interact with Snail in the nucleus on endogenous promoters. Endogenous frog protein has not been imaged, but the IBA is well founded. Supporting Evidence: file:XENLA/snai1/snai1-uniprot.txt SUBCELLULAR LOCATION: Nucleus PMID:18331720 Ajuba LIM proteins interact with Snail in the nucleus on endogenous E-cadherin promoters |
| GO:0005634 nucleus | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt subcellular-location IEA: nucleus. Reason: Consistent with nuclear transcriptional repressor activity. Supporting Evidence: file:XENLA/snai1/snai1-uniprot.txt SUBCELLULAR LOCATION: Nucleus |
| GO:0005634 nucleus | ISS GO_REF:0000024 | ACCEPT | Summary: ISS from mouse Snai1 (Q02085): nucleus. Reason: Mouse Snai1 is an experimentally nuclear repressor; transfer to the frog ortholog is sound. Supporting Evidence: file:XENLA/snai1/snai1-uniprot.txt SUBCELLULAR LOCATION: Nucleus |
| GO:0006355 regulation of DNA-templated transcription | IBA GO_REF:0000033 | ACCEPT | Summary: IBA: regulation of DNA-templated transcription. Reason: Correct but general; the direction (negative, Pol II) is captured by the experimental GO:0000122 row. P19382 appearing among its own sources reflects its experimental grounding, not circularity. Supporting Evidence: PMID:12490555 We show that Snail is required for neural crest specification and migration and that it works as a transcriptional repressor. |
| GO:0006355 regulation of DNA-templated transcription | IEA GO_REF:0000118 | ACCEPT | Summary: TreeGrafter IEA: regulation of DNA-templated transcription. Reason: Correct, general; see IBA row. Supporting Evidence: PMID:12490555 We show that Snail is required for neural crest specification and migration and that it works as a transcriptional repressor. |
| GO:0014029 neural crest formation | TAS PMID:15242799 Cardiac neural crest ablation alters Id2 gene expression in ... | MODIFY | Summary: AgBase TAS to neural crest formation citing Martinsen et al. 2004, a chick/Xenopus cardiac neural crest ablation study of Id2 expression. Reason: The cited abstract concerns Id2 expression after cardiac crest ablation and does not mention Snail; the same reference sources the TAS rows on snai2 and twist1. The biology is nevertheless sound at a more precise level. Snail1 is not a border specifier: Zic1 activates it directly, it acts upstream of Slug, FoxD3, Twist and Ets1, and in naive animal caps it induces all crest markers tested without neural-plate or mesoderm markers, i.e. it specifies crest identity. Following the convention applied to snai2, sox8, sox9-a and sox10 (the proposed neural plate border formation term for border-acting genes, GO:0014036 for specifiers), the term is narrowed to neural crest cell fate specification, which the IMP row already supports. The weak TAS reference should be replaced by the Xenopus experimental papers. Proposed replacements: neural crest cell fate specification Supporting Evidence: PMID:12490555 We show that Snail is able to induce the expression of Slug and all other neural crest markers tested (Zic5, FoxD3, Twist and Ets1) at the time of specification. PMID:12490555 This activation is observed in whole embryos and in animal caps, in the absence of neural plate and mesodermal markers. PMID:24360906 were highly and reproducibly activated either by Pax3 (snail2, twist1) or by Zic1 (snail1) in the presence of cycloheximide PMID:12490555 Snail lies upstream of Slug in the genetic cascade leading to neural crest formation |
| GO:0014036 neural crest cell fate specification | IEA GO_REF:0000117 | ACCEPT | Summary: ARBA IEA: neural crest cell fate specification. Reason: Matches the experimental evidence; this is the right crest layer for Snail1. Supporting Evidence: PMID:12490555 We show that Snail is able to induce the expression of Slug and all other neural crest markers tested (Zic5, FoxD3, Twist and Ets1) at the time of specification. PMID:12490555 Snail lies upstream of Slug in the genetic cascade leading to neural crest formation |
| GO:0014036 neural crest cell fate specification | IMP PMID:12490555 Snail precedes slug in the genetic cascade required for the ... | ACCEPT | Summary: Neural crest cell fate specification from Aybar et al. 2003 (inducible dominant-negative and activated Snail constructs; Slug rescue epistasis). Reason: Synthesised picture: snai1 is one of the first genes activated by Pax3/Zic1 in crest progenitors (with sox8 and myc), and Zic1 binds and activates an upstream snai1 element directly; it is expressed in the prospective crest before slug; inducible Snail is sufficient in whole embryos and naive caps to induce Slug, Zic5, FoxD3, Twist and Ets1 without neural plate or mesoderm markers (Slug cannot); and inhibiting Snail at specification stages removes crest markers, rescued by Slug, placing Snail1 upstream of Slug. This is the earliest crest-specifier layer, one step below the border pair. Core. Supporting Evidence: PMID:12490555 in Xenopus, Snail precedes Slug expression in this population PMID:23509273 Indeed, a group of early genes ( snail1 , sox8 , and myc ) was activated during early neurulation PMID:24360906 were highly and reproducibly activated either by Pax3 (snail2, twist1) or by Zic1 (snail1) in the presence of cycloheximide PMID:24360906 Zic1 binds to snail1 putative oligonucleotide PMID:12490555 We show that Snail is able to induce the expression of Slug and all other neural crest markers tested (Zic5, FoxD3, Twist and Ets1) at the time of specification. PMID:12490555 This activation is observed in whole embryos and in animal caps, in the absence of neural plate and mesodermal markers. PMID:12490555 Snail lies upstream of Slug in the genetic cascade leading to neural crest formation PMID:12490555 Slug alone is unable to induce other neural crest markers in animal cap assays |
| GO:0045892 negative regulation of DNA-templated transcription | IDA PMID:12490555 Snail precedes slug in the genetic cascade required for the ... | ACCEPT | Summary: Negative regulation of DNA-templated transcription, from the same repressor-fusion experiments. Reason: Correct parent of the GO:0000122 row from the same paper; redundant but not wrong. Supporting Evidence: PMID:12490555 We show that Snail is required for neural crest specification and migration and that it works as a transcriptional repressor. |
| GO:0001227 DNA-binding transcription repressor activity, RNA polymerase II-specific | IDA PMID:12490555 Snail precedes slug in the genetic cascade required for the ... | NEW | Summary: Snail1 is a sequence-specific Pol II transcriptional repressor. Reason: Fusion of the Xsnail zinc-finger region to an Engrailed repressor domain phenocopies Snail gain of function in the crest whereas an E1A-activator fusion antagonises it; Snail represses Delta1 at the crest border; SNAG recruits Ajuba LIM corepressors. Comparator (QuickGO 2026-10-07): mouse Snai1 (Q02085) and human SNAI1 (O95863) both carry GO:0001227 by IDA and IBA; frog snai2 was given the same term. The GOA set has only the generic GO:0000981. Supporting Evidence: PMID:12490555 We show that Snail is required for neural crest specification and migration and that it works as a transcriptional repressor. file:XENLA/snai1/snai1-deep-research-falcon.md a fusion of the Xsnail zinc-finger region to an Engrailed repression domain expanded neural-crest-marker expression, whereas fusion to an E1A activation domain inhibited those markers PMID:18331720 Here, we identify the Ajuba family of LIM proteins as functional corepressors of the Snail family via an interaction with the SNAG domain. file:XENLA/snai1/snai1-uniprot.txt Transcriptional repressor. Acts upstream of snai2/slug, zic5 and other neural crest markers in the specification of the neural crest and neural crest migration. |
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Download this section (compressed HTML)Q: Snail1 is co-expressed with, and required to maintain, the Oct/Sox/Vent pluripotency network and the competence of blastula animal-pole cells (Buitrago-Delgado 2015). No GO process term captures this competence role; should GO:0019827 stem cell population maintenance apply (the same question raised for id3-a and myc-a), or is a more specific term needed?
Q: Frog Snail1 is expressed in all early mesoderm and induced by mesoderm-inducing factors, and mouse Snai1 carries GO:0001707 mesoderm formation by IMP. Is there snai1-specific frog loss-of-function evidence (rather than loss of blastula competence) that would justify mesoderm formation or gastrulation terms for P19382?
Q: The AgBase TAS to GO:0014029 cites PMID:15242799, an Id2 cardiac crest paper that does not mention Snail (the same source as the snai2 and twist1 TAS rows). Should these rows be withdrawn at source?
Q: Lamprey has a single snail gene with flat expression dynamics across blastula and crest stages, like frog snai1, whereas frog snai2 rises monotonically like a definitive crest factor; in mouse, Snail rather than Slug marks premigratory crest. Which paralog carries the crest-specifier role is therefore lineage-specific: should Snai1 crest annotations be transferred by orthology at all?
Q: Does snai1.S (A0A1L8ELB6) share the experimental functions of snai1.L (P19382)? The dominant-negative zinc-finger reagents would not distinguish homeologs (or paralogs).
Experiment: Homeolog-resolved tagged-Snail1 CUT&RUN in blastula animal caps and in stage 12-14 neural folds, combined with RNA-seq of snai1 F0 CRISPR (both homeologs) explants, to define direct targets at each stage.
Hypothesis: Snail1 directly represses distinct target sets in blastula animal cells (maintaining competence) and in early crest progenitors (specification).
Type: ChIP-seq
Experiment: Single and combined F0 CRISPR knockouts of snai1 and snai2 scoring pluripotency markers at blastula, border and specifier markers at neural plate stages, and migration.
Hypothesis: snai1 and snai2 are partially redundant in crest specification, but snai1 is uniquely required for blastula competence.
Type: CRISPR knockout
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