Gene Ontology annotation through association of InterPro records with GO terms
Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity
Annotation inferences using phylogenetic trees
Gene Ontology annotation based on curation of immunofluorescence data
Gene Ontology annotation of human sequence-specific DNA binding transcription factors (DbTFs) based on the TFClass database
Combined Automated Annotation using Multiple IEA Methods
Deep research review of OTX2 function and biology
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OTX2 recognises bicoid-type homeobox sites in regulatory DNA, with TAATCC as the strongest reported in vitro motif.
"OTX2 recognizes bicoid-like homeobox sites in regulatory DNA."
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In Group 3 medulloblastoma OTX2 behaves as a pioneer-like factor, associating with SWI/SNF and coactivator complexes at distal enhancers.
"OTX2 associated with SWI/SNF components SMARCA4, SMARCA2 and SMARCC1 and with UTX, ASH2 and p300."
OTX2 regulates expression of DOPAchrome tautomerase in human retinal pigment epithelium.
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OTX2 occupies the human DCT promoter in vivo in retinal pigment epithelial cells.
"OTX2 binds to the DCT gene promoter in vivo, as judged by chromatin immunoprecipitation assays."
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OTX2 activates the DCT promoter through its cognate binding site in an RPE-restricted manner, establishing transcriptional activator activity.
"Transient expression assays revealed that OTX2 activated the DCT gene promoter through the OTX-2-binding site in an RPE-specific manner."
Genomic amplification of orthodenticle homologue 2 in medulloblastomas.
Emx2 homeodomain transcription factor interacts with eukaryotic translation initiation factor 4E (eIF4E) in the axons of olfactory sensory neurons.
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Human OTX2 protein binds eIF4E directly in GST pull-down assays, alongside Engrailed 2.
"Finally, we show that two other brain-expressed homeoproteins, Otx2 and Engrailed 2, also bind eIF4E, indicating that several homeoproteins may modulate eIF4E functions in the developing and adult nervous system."
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The construct used for the OTX2 pull-down was the human cDNA, so the binding result applies to the human protein.
"Mouse Emx1, Emx2 (pCMV-Emx2), and human Otx2 cDNAs were provided by A. Simeone"
The transcription factor Engrailed-2 guides retinal axons.
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OTX2 was assayed in this study as the specificity control and is internalised by retinal growth cones.
"To address this, we tested Otx2, another homeodomain transcription factor that shares the secretion, internalization and eIF4E-binding properties of En-2"
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The published conclusion is that OTX2 does not produce the divergent turning response that defines the guidance activity; it only weakly attracted both populations.
"Thus, unlike En-2, Otx2 does not elicit opposite turning responses in the two populations of retinal axons, indicating that En-2 acts specifically to induce these divergent behaviours."
Expression of the homeobox genes PAX6, OTX2, and OTX1 in the early human fetal retina.
Wnt1-lmx1a forms a novel autoregulatory loop and controls midbrain dopaminergic differentiation synergistically with the SHH-FoxA2 pathway.
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Otx2 acts combinatorially with Lmx1a and FoxA2 to enhance midbrain dopaminergic differentiation, which is the genetic interaction behind the IGI.
"Furthermore, coactivation of both Wnt1 and SHH pathways by exogenous expression of Lmx1a, Otx2, and FoxA2 synergistically enhanced the differentiation of ESCs to mDA neurons."
SOX9, through interaction with microphthalmia-associated transcription factor (MITF) and OTX2, regulates BEST1 expression in the retinal pigment epithelium.
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OTX2 physically interacts with SOX9 and MITF and the three synergistically activate the human BEST1 promoter.
"Importantly, SOX9 physically interacted with MITF and OTX2 and orchestrated synergistic activation of the BEST1 promoter with the paired SOX site playing essential roles."
Differentiation of human epidermal neural crest stem cells (hEPI-NCSC) into virtually homogenous populations of dopaminergic neurons.
Wnt signaling in midbrain dopaminergic neuron development and regenerative medicine for Parkinson's disease.
Impact of cytosine methylation on DNA binding specificities of human transcription factors
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Methyl-SELEX across 542 human transcription factors places OTX2 among the extended homeodomain factors that prefer CpG-methylated binding sites.
"we found that there are also many TFs that prefer CpG-methylated sequences. Most of these are in the extended homeodomain family."
Forebrain and midbrain regions are deleted in Otx2-/- mutants due to a defective anterior neuroectoderm specification during gastrulation.
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Mouse Otx2 null embryos lack the forebrain and midbrain entirely.
"By 9.5 dpc, homozygous mutant embryos are characterized by the absence of forebrain and midbrain regions."
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The defect is a failure of anterior neuroectoderm specification during gastrulation, not later degeneration.
"These data suggest that Otx2 expression in endomesoderm and ectoderm is required for anterior neuroectoderm specification."
Mouse Otx2 functions in the formation and patterning of rostral head.
A targeted mouse Otx2 mutation leads to severe defects in gastrulation and formation of axial mesoderm and to deletion of rostral brain.
A role for Gbx2 in repression of Otx2 and positioning the mid/hindbrain organizer.
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GBX2 represses OTX2 and the sharp caudal OTX2 border positions the midbrain-hindbrain organizer.
"We propose that formation of a normal MHB organizer depends on a sharp Otx2 caudal border and that Gbx2 is required to position and sharpen this border."
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Shifting the OTX2 border by ectopic Gbx2 relocates the organizer, showing the boundary is instructive.
"we transiently expressed Gbx2 in the caudal Otx2 domain and found that the Otx2 caudal border was indeed shifted rostrally and a normal appearing organizer formed at this new Otx2 border."
Differentiation of cerebellar cell identities in absence of Fgf signalling in zebrafish Otx morphants.
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Loss of Otx function in zebrafish transforms the presumptive midbrain into an extended rhombomere 1, so Otx sets the caudal limit of midbrain identity.
"lack of Otx function in zebrafish leads to transformation of the presumptive mesencephalon into an extended rhombomere 1 (r1)"
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Fgf8 maintains rather than induces the posterior Otx boundary, so the boundary's position is a property of the Otx domain itself.
"Fgf8 is required to maintain, rather than induce, the posterior boundary of Otx expression."
Otx2 homeobox gene controls retinal photoreceptor cell fate and pineal gland development.
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Conditional Otx2 loss converts differentiating photoreceptors to amacrine-like neurons and abolishes pinealocytes.
"Otx2-deficiency converted differentiating photoreceptor cells to amacrine-like neurons and led to a total lack of pinealocytes in the pineal gland."
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OTX2 acts through direct transactivation of CRX, and is sufficient to drive photoreceptor fate.
"We also found that Otx2 transactivates the cone-rod homeobox gene Crx, which is required for terminal differentiation and maintenance of photoreceptor cells."
Experience-dependent transfer of Otx2 homeoprotein into the visual cortex activates postnatal plasticity.
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OTX2 transfers non-cell-autonomously into cortical parvalbumin interneurons in response to visual experience and sets critical-period timing.
"Visual experience promoted the accumulation of non-cell-autonomous Otx2 in PV-cells, and cortical infusion of exogenous Otx2 accelerated both PV-cell development and critical period timing."
Congenital pituitary hypoplasia model demonstrates hypothalamic OTX2 regulation of pituitary progenitor cells.
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Hypothalamic OTX2 acts non-cell-autonomously on pituitary progenitors by controlling FGF10, which induces LHX3 in oral ectoderm.
"OTX2 in hypothalamus, not in oral ectoderm, was essential for progenitor cell maintenance by regulating LHX3 expression in oral ectoderm via FGF10 expression in the hypothalamus."
The phenotypic spectrum associated with OTX2 mutations in humans.
OTX2 Activity at Distal Regulatory Elements Shapes the Chromatin Landscape of Group 3 Medulloblastoma.
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OTX2 occupancy is overwhelmingly at distal enhancers rather than promoters.
"OTX2 binding sites were found at putative enhancer regions (91%) while only a small fraction were present at promoters (9%)"
A group 3 medulloblastoma stem cell program is maintained by OTX2-mediated alternative splicing.
Two parallel neural ectoderm progenitors contribute to the developing brain.
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OTX2-positive anterior neural ectoderm and GBX2-positive posterior neural ectoderm arise in parallel during gastrulation as the forebrain/midbrain and hindbrain progenitors respectively.
"Two parallel brain progenitors emerge simultaneously during gastrulation: anterior neural ectoderm (forebrain/midbrain progenitor) and posterior neural ectoderm (hindbrain progenitor)."
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The two populations are already lineage committed, not merely differently positioned.
"Differentiation of human pluripotent stem cells into anterior or posterior neural ectoderm-like cells revealed these were lineage committed to forebrain/midbrain versus hindbrain fates, respectively."
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Commitment has a chromatin correlate that precedes overt regional identity.
"They harbored diverging chromatin landscapes foreshadowing future forebrain/midbrain versus hindbrain identities."