Sox9a is one of two zebrafish co-orthologs of vertebrate SOX9, produced by the teleost-specific genome duplication. It is an SRY-related HMG-box (SoxE group) transcription factor: its HMG box binds the Sox consensus DNA motif and a central transactivation region activates transcription of target genes such as col2a1a and col11a2. Sox9a is expressed in cranial neural crest-derived chondrogenic mesenchyme of the neurocranium and pharyngeal arches, the pectoral girdle (scapulocoracoid), otic placode, hindbrain glial progenitors and, in adults, in many tissues including testis Sertoli cells. It is essential for chondrocyte differentiation and for the stacking and shaping of cartilage condensations: sox9a (jellyfish) mutants lack most craniofacial and pectoral girdle cartilage. It also contributes, partly redundantly with sox9b, dlx3b/dlx4b and sox10, to otic placode and inner ear development, and is required for oligodendrocyte progenitor and astroglial development in the hindbrain. The two co-orthologs share a near-identical HMG box but divide the ancestral SOX9 expression domains between them.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000122 negative regulation of transcription by RNA polymerase II | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: IBA: negative regulation of transcription by RNA polymerase II, propagated from PTN000741645 (human SOX9 donor). Reason: SOX9 is chiefly a transcriptional activator but represses some targets in mammals; the Sox9a HMG box is 98.6% identical to human SOX9 (file:DANRE/sox9a/sox9a-bioinformatics/RESULTS.md), so inheritance of this capacity is plausible and there is no evidence of loss in the sox9a lineage. No zebrafish experiment directly shows Sox9a-mediated repression, so it is kept as a non-core inherited property. Supporting Evidence: PMID:11180959 We tested different domains for transactivation potential and identified a potential activation domain located in the middle of both Sox9a and Sox9b. |
| GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding | IBA GO_REF:0000033 | ACCEPT | Summary: IBA: RNA polymerase II cis-regulatory region sequence-specific DNA binding. Reason: Sox9a binds HMG consensus sites in vitro and occupies regulatory regions of target genes in ChIP assays; the HMG box is conserved with human SOX9. Supporting Evidence: PMID:11180959 Both Sox9a and Sox9b proteins bind to the HMG consensus DNA sequences in vitro. PMID:25568117 ChIP-PCR assay verified 11 of 21 genes for Atoh1a and 11 of 18 genes for Sox9a as reproducible targets |
| 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: Core molecular function. Sox9a binds DNA and carries a transactivation domain, and loss of sox9a abolishes expression of Sox9 target genes such as col2a1 and col11a2 in cartilage. Supporting Evidence: PMID:11180959 Both Sox9a and Sox9b proteins bind to the HMG consensus DNA sequences in vitro. PMID:11180959 We tested different domains for transactivation potential and identified a potential activation domain located in the middle of both Sox9a and Sox9b. PMID:12397114 Homozygous mutant embryos had greatly reduced quantities of col2a1 message, the major collagen of cartilage. PMID:19210963 In sox9a mutants, expression of col11a2 disappeared from the neurocranium and pharyngeal arches, and was reduced in the opercle |
| GO:0002009 morphogenesis of an epithelium | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: IBA: morphogenesis of an epithelium (PTN000741645; donors include both zebrafish sox9a and sox9b). Reason: Sox9a contributes to formation of the otic epithelium together with dlx3b/dlx4b and sox9b; the term is broad and not the central role of the gene. Supporting Evidence: PMID:12668634 Removal of dlx3b, dlx4b and sox9a genes together also blocks ear development, although a few residual cells form an otic epithelium. PMID:15689370 Ears are somewhat reduced in each single mutant but are mostly absent in the double mutant. |
| GO:0002062 chondrocyte differentiation | IBA GO_REF:0000033 | ACCEPT | Summary: IBA: chondrocyte differentiation. Reason: Central role: sox9a mutants lack overt cartilage differentiation and chondrocyte stacking, with loss of col2a1. Supporting Evidence: PMID:12397114 These studies show that jef (sox9a) is essential for both morphogenesis of condensations and overt cartilage differentiation. PMID:12397114 Homozygous mutant embryos had greatly reduced quantities of col2a1 message, the major collagen of cartilage. PMID:15689370 Chondrocytes failed to stack in sox9a mutants, failed to attain proper numbers in sox9b mutants and failed in both morphogenetic processes in double mutants. |
| GO:0003677 DNA binding | IEA GO_REF:0000104 | ACCEPT | Summary: IEA (UniRule): DNA binding. Reason: Correct but general; the more informative sequence-specific cis-regulatory DNA binding term is also accepted. Supporting Evidence: PMID:11180959 Both Sox9a and Sox9b proteins bind to the HMG consensus DNA sequences in vitro. |
| GO:0003682 chromatin binding | IDA PMID:25568117 Fgf-signaling-dependent Sox9a and Atoh1a regulate otic neura... | ACCEPT | Summary: IDA: chromatin binding, from ChIP-seq/ChIP-PCR of Myc-tagged Sox9a in zebrafish embryos. Reason: ChIP of tagged Sox9a identified and verified occupied target loci (e.g. eya2, tlx2), which supports chromatin binding. The more specific sequence-specific cis-regulatory binding term (GO:0000978) is the core function; this annotation is consistent with it. Supporting Evidence: PMID:25568117 ChIP-PCR assay verified 11 of 21 genes for Atoh1a and 11 of 18 genes for Sox9a as reproducible targets |
| GO:0005515 protein binding | IPI PMID:25617839 Ewing sarcoma ewsa protein regulates chondrogenesis of Mecke... | REMOVE | Summary: IPI: protein binding, Ewsa co-immunoprecipitated with Sox9 in zebrafish embryo lysates. Reason: Generic protein binding is uninformative. The removal does not dispute the Ewsa-Sox9 interaction. Note also that the co-IP used a commercial anti-SOX9 antibody, so the cached text does not show which zebrafish copy (Sox9a or Sox9b) was precipitated; no more specific MF can be assigned from this evidence. Supporting Evidence: PMID:25617839 The co-IP experiment for zebrafish Ewsa and Sox9 was performed with 27 hpf zebrafish embryos. PMID:25617839 anti-Sox9 (1:100)(Abcam, MA) |
| GO:0005634 nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: IBA: nucleus (is_active_in). Reason: Sox9a is a DNA-binding transcription factor with a conserved HMG box that carries the Sox nuclear localization signals; nuclear activity is expected and consistent with its target-gene occupancy in ChIP. Supporting Evidence: PMID:11180959 Both Sox9a and Sox9b proteins bind to the HMG consensus DNA sequences in vitro. PMID:25568117 ChIP-PCR assay verified 11 of 21 genes for Atoh1a and 11 of 18 genes for Sox9a as reproducible targets |
| GO:0005634 nucleus | IEA GO_REF:0000120 | ACCEPT | Summary: IEA: nucleus (UniProt subcellular location mapping). Reason: Consistent with the IBA and the transcription-factor function. Supporting Evidence: PMID:11180959 Both Sox9a and Sox9b proteins bind to the HMG consensus DNA sequences in vitro. |
| GO:0005737 cytoplasm | IMP PMID:12397114 A zebrafish sox9 gene required for cartilage morphogenesis. | MARK AS OVER ANNOTATED | Summary: IMP: cytoplasm, from Yan et al. 2002 (jef mutant / splice-blocking morpholinos). Reason: The observation in the cited paper concerns the sox9a mRNA, not the protein: splice-blocking morpholinos caused unspliced sox9a transcript to accumulate in the nucleus, which the authors used as an assay for morpholino efficacy. That is transcript processing/export, not where the Sox9a protein acts. Independent work (Sun et al. 2013) reports a regulated cytoplasmic pool of Sox9a protein in juvenile gonad stromal cells alongside nuclear Sox9a, so a cytoplasmic location is not impossible, but Sox9a executes its transcription-factor function in the nucleus and the cited evidence does not support the protein-level claim. Marked as over-annotation rather than removed because of the independent gonadal data. Supporting Evidence: PMID:12397114 Inhibiting splicing of the sox9a transcript in wild-type embryos with splice site-directed morpholino antisense oligonucleotides produced a phenotype like jef mutant larvae, and caused sox9a transcript to accumulate in the nucleus PMID:24263104 After MKI treatment, levels of sox9a and p-Erk1/2 were dramatically decreased in the cytoplasm, whereas nuclear sox9a and p-Erk1/2 showed little reduction. |
| GO:0005737 cytoplasm | IMP PMID:12397114 A zebrafish sox9 gene required for cartilage morphogenesis. | MARK AS OVER ANNOTATED | Summary: IMP: cytoplasm, from Yan et al. 2002 (jef mutant / splice-blocking morpholinos). Reason: The observation in the cited paper concerns the sox9a mRNA, not the protein: splice-blocking morpholinos caused unspliced sox9a transcript to accumulate in the nucleus, which the authors used as an assay for morpholino efficacy. That is transcript processing/export, not where the Sox9a protein acts. Independent work (Sun et al. 2013) reports a regulated cytoplasmic pool of Sox9a protein in juvenile gonad stromal cells alongside nuclear Sox9a, so a cytoplasmic location is not impossible, but Sox9a executes its transcription-factor function in the nucleus and the cited evidence does not support the protein-level claim. Marked as over-annotation rather than removed because of the independent gonadal data. Supporting Evidence: PMID:12397114 Inhibiting splicing of the sox9a transcript in wild-type embryos with splice site-directed morpholino antisense oligonucleotides produced a phenotype like jef mutant larvae, and caused sox9a transcript to accumulate in the nucleus PMID:24263104 After MKI treatment, levels of sox9a and p-Erk1/2 were dramatically decreased in the cytoplasm, whereas nuclear sox9a and p-Erk1/2 showed little reduction. |
| GO:0007507 heart development | IBA GO_REF:0000033 | MARK AS OVER ANNOTATED | Summary: IBA: heart development (PTN002910118; zebrafish donor is sox9b, ZDB-GENE-001103-2). Reason: The cardiac role of the ancestral SOX9 gene went to sox9b in zebrafish: sox9b is required for proepicardium, epicardium and valve formation, whereas an effective sox9a morpholino did not cause cardiac malformations. The IBA propagates the function to both co-orthologs, which is correct for the ancestral node but not supported for sox9a, which appears to have lost this subfunction by expression partition. Morpholino negative evidence is not conclusive, so this is marked as an over-annotation rather than removed. Propagation Review Root cause: PROPAGATION BAD Failure modes: FUNCTIONAL DIVERGENCE CONTEXT OR TISSUE MISMATCH Sources checked: PANTHER:PTN002910118 SUPPORTS SOURCE BUT NOT TARGET Ancestral SOX9 node; the cardiac role is sound for the node and for sox9b, but after the TGD the cardiac expression domain appears to have been retained only by sox9b. ZFIN:ZDB-GENE-001103-2 · sox9b SUPPORTS SOURCE BUT NOT TARGET Paralog donor with IMP evidence for proepicardium, epicardium and valve development; the sox9a morpholino control in the same study showed no cardiac defect. Supporting Evidence: PMID:23775563 Knock down of sox9a expression did not cause cardiac malformations, or defects in epicardium development. PMID:23775563 Furthermore, sox9b is required for PE, epicardium, and valve formation. PMID:15689370 Analysis of mutant phenotypes strongly supports the interpretation that ancestral gene functions partitioned spatially and temporally between Sox9 co-orthologs. |
| GO:0030916 otic vesicle formation | IGI PMID:15689370 A pair of Sox: distinct and overlapping functions of zebrafi... | KEEP AS NON CORE | Summary: IGI: otic vesicle formation (sox9a;sox9b double mutant). Reason: Ears are reduced in each single mutant and mostly absent in double mutants, so sox9a acts partly redundantly with sox9b in otic vesicle formation. Supporting Evidence: PMID:15689370 Ears are somewhat reduced in each single mutant but are mostly absent in the double mutant. |
| GO:0032332 positive regulation of chondrocyte differentiation | IBA GO_REF:0000033 | ACCEPT | Summary: IBA: positive regulation of chondrocyte differentiation. Reason: Sox9a promotes chondrocyte differentiation by activating cartilage matrix genes; the IBA is well supported by the zebrafish mutant data. Supporting Evidence: PMID:12397114 These studies show that jef (sox9a) is essential for both morphogenesis of condensations and overt cartilage differentiation. PMID:12397114 Homozygous mutant embryos had greatly reduced quantities of col2a1 message, the major collagen of cartilage. |
| GO:0033339 pectoral fin development | IMP PMID:9007245 Genetic analysis of fin formation in the zebrafish, Danio re... | KEEP AS NON CORE | Summary: IMP: pectoral fin development, from the Tuebingen fin mutant screen (van Eeden et al. 1996). Reason: Only the abstract is cached and it does not name jellyfish; the curator presumably used the full text. The annotation is consistent with the loss of pectoral girdle cartilage in sox9a (jef) mutants reported independently, so it is kept, as a non-core developmental role that follows from its chondrogenic function. Supporting Evidence: PMID:12397114 lack cartilage elements of the neurocranium, pharyngeal arches, and pectoral girdle similar to humans with campomelic dysplasia PMID:19210963 In the wild-type pectoral apparatus, sox9a is expressed strongly in the scapulocoracoid of the pectoral girldle but was weaker in the blade of the fin bud and did not appear in the cleithrum of the pectoral girdle. |
| GO:0035118 embryonic pectoral fin morphogenesis | IMP PMID:12397114 A zebrafish sox9 gene required for cartilage morphogenesis. | KEEP AS NON CORE | Summary: IMP: embryonic pectoral fin morphogenesis. Reason: sox9a mutants and morphants lack pectoral girdle cartilage, and each co-ortholog is required for a distinct subset of the pectoral appendage. Kept as a non-core organ-level consequence of its chondrogenic function. Supporting Evidence: PMID:12397114 lack cartilage elements of the neurocranium, pharyngeal arches, and pectoral girdle similar to humans with campomelic dysplasia PMID:15689370 Distinct subsets of the craniofacial skeleton, otic placode and pectoral appendage express each gene, and are defective in each single mutant. |
| GO:0035118 embryonic pectoral fin morphogenesis | IMP PMID:12397114 A zebrafish sox9 gene required for cartilage morphogenesis. | KEEP AS NON CORE | Summary: IMP: embryonic pectoral fin morphogenesis. Reason: sox9a mutants and morphants lack pectoral girdle cartilage, and each co-ortholog is required for a distinct subset of the pectoral appendage. Kept as a non-core organ-level consequence of its chondrogenic function. Supporting Evidence: PMID:12397114 lack cartilage elements of the neurocranium, pharyngeal arches, and pectoral girdle similar to humans with campomelic dysplasia PMID:15689370 Distinct subsets of the craniofacial skeleton, otic placode and pectoral appendage express each gene, and are defective in each single mutant. |
| GO:0035118 embryonic pectoral fin morphogenesis | IMP PMID:15689370 A pair of Sox: distinct and overlapping functions of zebrafi... | KEEP AS NON CORE | Summary: IMP: embryonic pectoral fin morphogenesis. Reason: sox9a mutants and morphants lack pectoral girdle cartilage, and each co-ortholog is required for a distinct subset of the pectoral appendage. Kept as a non-core organ-level consequence of its chondrogenic function. Supporting Evidence: PMID:12397114 lack cartilage elements of the neurocranium, pharyngeal arches, and pectoral girdle similar to humans with campomelic dysplasia PMID:15689370 Distinct subsets of the craniofacial skeleton, otic placode and pectoral appendage express each gene, and are defective in each single mutant. |
| GO:0043049 otic placode formation | IGI PMID:12668634 Fgf3 and Fgf8 dependent and independent transcription factor... | KEEP AS NON CORE | Summary: IGI: otic placode formation (Df(b380) deletion removing dlx3b, dlx4b and sox9a, with Fgf pathway genes). Reason: The genetic evidence is from combined loss of several genes, so sox9a is one of several partly redundant contributors; supported but not core. Supporting Evidence: PMID:12668634 Removal of dlx3b, dlx4b and sox9a genes together also blocks ear development, although a few residual cells form an otic epithelium. PMID:12668634 These cells fail to form if sox9b function is also blocked. PMID:12668634 Expression of sox9a but not dlx3b, dlx4b or sox9b requires Fgf3 and Fgf8. |
| GO:0048708 astrocyte differentiation | IMP PMID:20023158 FGF-receptor signalling controls neural cell diversity in th... | KEEP AS NON CORE | Summary: IMP: astrocyte differentiation (sox9a tw37 mutant; loss of GS-positive astroglia in hindbrain). Reason: Full text shows sox9a is required for GS-positive astroglia in the hindbrain, a conserved SoxE gliogenic role. Non-core relative to chondrogenesis. Supporting Evidence: PMID:20023158 We have shown that in the zebrafish hindbrain, sox9a is necessary for the generation of both OLPs and GS-positive astroglia, supporting a phylogenetically conserved role. |
| GO:0048709 oligodendrocyte differentiation | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: IBA: oligodendrocyte differentiation (donor includes zebrafish sox9a itself). Reason: Sox9a being among the donors reflects its own experimental support (Esain et al. 2010), which is appropriate for an IBA. Kept as non-core. Supporting Evidence: PMID:20023158 We have shown that in the zebrafish hindbrain, sox9a is necessary for the generation of both OLPs and GS-positive astroglia, supporting a phylogenetically conserved role. |
| GO:0048709 oligodendrocyte differentiation | IMP PMID:20023158 FGF-receptor signalling controls neural cell diversity in th... | KEEP AS NON CORE | Summary: IMP: oligodendrocyte differentiation (sox9a mutant; reduced OLP markers). Reason: Sox9a is needed for oligodendrocyte progenitor generation in the hindbrain; residual marker expression is attributed to sox9b. Supporting Evidence: PMID:20023158 We have shown that in the zebrafish hindbrain, sox9a is necessary for the generation of both OLPs and GS-positive astroglia, supporting a phylogenetically conserved role. PMID:20023158 residual expression of glial markers in these mutants is probably due to the sox9b co-orthologue, which has an overlapping expression profile. |
| GO:0048839 inner ear development | IGI PMID:19132125 A zebrafish model for Waardenburg syndrome type IV reveals d... | KEEP AS NON CORE | Summary: IGI: inner ear development (with sox10 mutant and sox9 morpholinos). Reason: SoxE genes sox9a, sox9b and sox10 act redundantly to maintain sox10 and restrict fgf8 expression in the otic vesicle. Supporting Evidence: PMID:19132125 they act redundantly to maintain sox10 expression throughout otic tissue and to restrict fgf8 expression to anterior macula regions |
| GO:0048839 inner ear development | IMP PMID:19132125 A zebrafish model for Waardenburg syndrome type IV reveals d... | KEEP AS NON CORE | Summary: IMP: inner ear development (morpholinos). Reason: As above; the full text is not cached, but the abstract supports a redundant requirement for group E sox genes in otic patterning. Supporting Evidence: PMID:19132125 they act redundantly to maintain sox10 expression throughout otic tissue and to restrict fgf8 expression to anterior macula regions |
| GO:0048839 inner ear development | IMP PMID:25568117 Fgf-signaling-dependent Sox9a and Atoh1a regulate otic neura... | KEEP AS NON CORE | Summary: IMP: inner ear development (sox9a morpholino reduces statoacoustic ganglion). Reason: Sox9a knockdown reduces neurod expression and statoacoustic ganglion size; Sox9a acts downstream of Fgf signalling in otic neurogenesis. Supporting Evidence: PMID:25568117 When Sox9a function was knocked down by MO, neurod expression and SAG area were reduced PMID:25568117 Sox9a and Atoh1a act downstream of Fgfr-Akt signaling to specify and/or maintain the otic neuron fate during the early segmentation stage. |
| GO:0051216 cartilage development | IMP PMID:12397114 A zebrafish sox9 gene required for cartilage morphogenesis. | ACCEPT | Summary: IMP: cartilage development. Reason: Core role: loss of sox9a (mutant or morpholino) eliminates most craniofacial and pectoral girdle cartilage. Supporting Evidence: PMID:12397114 These studies show that jef (sox9a) is essential for both morphogenesis of condensations and overt cartilage differentiation. PMID:12397114 lack cartilage elements of the neurocranium, pharyngeal arches, and pectoral girdle similar to humans with campomelic dysplasia file:DANRE/sox9a/sox9a-deep-research-falcon.md Alcian-blue staining showed loss of all neurocranial cartilage and most pharyngeal-arch cartilage. |
| GO:0051216 cartilage development | IMP PMID:12397114 A zebrafish sox9 gene required for cartilage morphogenesis. | ACCEPT | Summary: IMP: cartilage development. Reason: Core role: loss of sox9a (mutant or morpholino) eliminates most craniofacial and pectoral girdle cartilage. Supporting Evidence: PMID:12397114 These studies show that jef (sox9a) is essential for both morphogenesis of condensations and overt cartilage differentiation. |
| GO:0051216 cartilage development | IMP PMID:15689370 A pair of Sox: distinct and overlapping functions of zebrafi... | ACCEPT | Summary: IMP: cartilage development. Reason: Core role: loss of sox9a (mutant or morpholino) eliminates most craniofacial and pectoral girdle cartilage. Supporting Evidence: PMID:15689370 Chondrocytes failed to stack in sox9a mutants, failed to attain proper numbers in sox9b mutants and failed in both morphogenetic processes in double mutants. PMID:15689370 Distinct subsets of the craniofacial skeleton, otic placode and pectoral appendage express each gene, and are defective in each single mutant. |
| GO:0051216 cartilage development | IMP PMID:18950725 Sox9a regulation of ff1a in zebrafish (Danio rerio) suggests... | ACCEPT | Summary: IMP: cartilage development. Reason: Core role: loss of sox9a (mutant or morpholino) eliminates most craniofacial and pectoral girdle cartilage. Supporting Evidence: PMID:18950725 blocking translation of either sox9a or ff1a also blocked cartilage formation. |
| GO:0051216 cartilage development | IMP PMID:18950725 Sox9a regulation of ff1a in zebrafish (Danio rerio) suggests... | ACCEPT | Summary: IMP: cartilage development. Reason: Core role: loss of sox9a (mutant or morpholino) eliminates most craniofacial and pectoral girdle cartilage. Supporting Evidence: PMID:18950725 blocking translation of either sox9a or ff1a also blocked cartilage formation. |
| GO:0060536 cartilage morphogenesis | IMP PMID:9007254 Jaw and branchial arch mutants in zebrafish II: anterior arc... | ACCEPT | Summary: IMP: cartilage morphogenesis (jellyfish mutant, Piotrowski et al. 1996). Reason: The jellyfish mutant, later shown to be sox9a, lacks almost all cartilage; Yan et al. 2002 showed Sox9a is needed for morphogenetic behaviours of condensations (stacking, individuation, shaping). Supporting Evidence: PMID:9007254 jellyfish mutant larvae are characterized by a severe reduction of all cartilaginous elements, leaving only two pieces in the position of the ceratohyal cartilages. PMID:12397114 We show that two alleles of jef contain mutations in sox9a, one of two zebrafish orthologs of the human transcription factor SOX9. PMID:12397114 These studies show that jef (sox9a) is essential for both morphogenesis of condensations and overt cartilage differentiation. |
| GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific | IDA PMID:11180959 Two sox9 genes on duplicated zebrafish chromosomes: expressi... | NEW | Summary: Proposed: Sox9a is a sequence-specific transcriptional activator. Reason: Chiang et al. 2001 showed that both zebrafish Sox9 proteins bind HMG consensus DNA and mapped a transactivation domain in the middle of each protein; the title describes them as similar transcription activators. Sox9a is required for expression of the SOX9 target genes col2a1 and col11a2. This refines the accepted GO:0000981 IBA. Proposed identically for sox9b, since the evidence covers both proteins. Supporting Evidence: PMID:11180959 Both Sox9a and Sox9b proteins bind to the HMG consensus DNA sequences in vitro. PMID:11180959 We tested different domains for transactivation potential and identified a potential activation domain located in the middle of both Sox9a and Sox9b. PMID:19210963 After the sox9 gene duplication event, regulatory elements controlling the expression of sox9 co-orthologs apparently partitioned in a tissue-specific fashion, but the Sox9 proteins encoded by sox9a and sox9b retained the ability to regulate col11a2, presumably by binding to regulatory sites for the col11a2 gene. |
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Download this section (compressed HTML)Q: Do Sox9a and Sox9b differ in transactivation strength or partner choice (e.g. with Sox5/Sox6 or other cofactors), given that divergence between the copies is concentrated outside the HMG box?
Q: Is the absence of a cardiac role for sox9a an expression-level loss (no cardiac cis-regulatory elements) or would Sox9a protein substitute for Sox9b if expressed in the heart?
Q: Which Sox9 copy did the Ewsa co-immunoprecipitation (PMID:25617839) detect, given a commercial anti-SOX9 antibody was used?
Experiment: Cross-rescue: express sox9a coding sequence from sox9b regulatory elements (knock-in or BAC) in sox9b fh313 mutants and test rescue of ductal, cardiac and cartilage phenotypes, to separate expression partition from protein divergence.
Experiment: Compare genome-wide occupancy (ChIP-seq/CUT&RUN) of tagged Sox9a and Sox9b in the same cell type (e.g. pharyngeal chondrocytes) to test whether target specificity differs.
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