Affinage

OLIG2

Oligodendrocyte transcription factor 2 · UniProt Q13516

Length
323 aa
Mass
32.4 kDa
Annotated
2026-04-29
100 papers in source corpus 38 papers cited in narrative 38 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

OLIG2 is a basic helix-loop-helix (bHLH) transcription factor that serves as a master regulator of neural progenitor fate, coupling the sequential specification of motor neurons and oligodendrocytes while suppressing astrocytic and neuronal alternative fates in the vertebrate CNS. Phosphorylation at S147 in the HLH domain promotes OLIG2 homodimerization and motor neuron specification, whereas dephosphorylation at this site shifts dimerization toward heterodimers with partners such as Neurogenin2 and TCF4 to drive oligodendrocyte precursor genesis and terminal oligodendrocyte differentiation (PMID:21382552, PMID:32266943). A separate N-terminal triple serine motif (S10/S13/S14), phosphorylated by a sequential GSK3β–CK2–CDK1/2 cascade, directs OLIG2 to active chromatin where it antagonizes p53-dependent cell cycle arrest—directly repressing p21WAF1/CIP1 and recruiting SETDB1 to deposit H3K9me3 on differentiation genes such as Sox11—thereby sustaining progenitor proliferation in both normal development and glioma (PMID:28355568, PMID:24948806, PMID:17296553, PMID:35301318). OLIG2 triplication contributes to GABAergic interneuron overproduction in Down syndrome, and genetic normalization of Olig2 dosage rescues the interneuron imbalance (PMID:20639873, PMID:31130512).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 2000 Medium

    Initial cloning of OLIG2 (as BHLHB1) established it as a neural-restricted bHLH factor capable of repressing E2A-mediated transcription, providing the first evidence that it functions as a transcriptional repressor.

    Evidence Transcriptional reporter assays in fibroblasts and T cells; chromosomal translocation breakpoint cloning

    PMID:10737801

    Open questions at the time
    • No endogenous neural function demonstrated
    • Repressor mechanism not defined beyond E2A antagonism
  2. 2001 High

    Gain-of-function experiments in chick spinal cord demonstrated that OLIG2 acts as a transcriptional repressor that, depending on co-expressed factors (e.g., NKX2.2), can direct either motor neuron or oligodendrocyte differentiation, resolving how one factor specifies two distinct lineages.

    Evidence In ovo misexpression in chick spinal cord; transcriptional repressor assays

    PMID:11567617

    Open questions at the time
    • Mechanism of partner-dependent fate switching unknown
    • Direct transcriptional targets not identified
  3. 2002 High

    Loss-of-function studies across mouse and zebrafish established that OLIG2 is essential and non-redundant for motor neuron and oligodendrocyte genesis from pMN domain progenitors, with Olig2-null cells converting to astrocytes or V2 interneurons.

    Evidence Olig2 single and Olig1/2 double knockout mice; zebrafish morpholino knockdown and overexpression; lineage marker analysis

    PMID:11955447 PMID:12121626 PMID:12167410

    Open questions at the time
    • Molecular basis for temporal MN-to-OLP switch unresolved
    • Cell-autonomous vs. non-autonomous contributions unclear
  4. 2003 High

    Identification of a physical OLIG2–NKX2.2 protein complex provided the first direct interaction partner, suggesting a mechanism for how their co-expression promotes oligodendrocyte specification, though the complex alone was insufficient.

    Evidence Reciprocal co-immunoprecipitation in mammalian cells and yeast two-hybrid with deletion mapping

    PMID:14573534

    Open questions at the time
    • Functional role of the complex in chromatin or transcription not defined
    • No genome-wide target analysis
  5. 2004 High

    Demonstrating that OLIG2 blocks p300–STAT3 complex formation explained how OLIG2 suppresses astrocytic differentiation at the mechanistic level, linking its repressor function to inhibition of the JAK-STAT–GFAP pathway.

    Evidence Co-immunoprecipitation of p300-STAT3; GFAP promoter luciferase assay; forced expression/knockdown in neuroepithelial cells

    PMID:14576772

    Open questions at the time
    • Whether OLIG2 directly binds p300 or disrupts complex indirectly unclear
    • In vivo validation not performed
  6. 2006 Medium

    Discovery that OLIG2 activates p27Kip1 transcription in glioma cells and that OLIG2 cooperates with Zfp488 for oligodendrocyte differentiation expanded the functional repertoire, revealing context-dependent activator versus repressor roles and additional interaction partners.

    Evidence Tet-off OLIG2 expression, p27Kip1 promoter reporter/EMSA/siRNA rescue; Zfp488 co-IP plus in ovo misexpression

    PMID:16554441 PMID:16908628

    Open questions at the time
    • p27Kip1 activation contradicts its general repressor activity—context-dependency mechanism unresolved
    • Zfp488 interaction confirmed by single lab only
  7. 2007 High

    Identification of p21WAF1/CIP1 as a direct transcriptional target repressed by OLIG2 established the molecular basis of OLIG2's pro-proliferative function in both neural progenitors and glioma, linking OLIG2 to cell cycle control.

    Evidence Conditional Olig2 KO in murine glioma model; ChIP and promoter reporter assays for p21

    PMID:17296553

    Open questions at the time
    • No genome-wide identification of other direct proliferation targets at this stage
    • Relationship between p21 repression and p53 pathway not yet connected
  8. 2007 High

    Studies on brain injury revealed that OLIG2 undergoes regulated nucleocytoplasmic translocation controlled by BMP/Notch signaling, and that OLIG2 is required for white matter astrocyte development and reactive astrocyte proliferation, extending its roles beyond the oligodendrocyte–motor neuron binary.

    Evidence Conditional Olig2 KO with multiple Cre lines; stab-wound injury models in rats; DAPT pharmacological inhibition; BrdU proliferation assay

    PMID:16330768 PMID:17428828 PMID:17510983 PMID:18945906

    Open questions at the time
    • Molecular mechanism of nucleocytoplasmic translocation not defined
    • Direct target genes in reactive astrocytes unknown
  9. 2011 High

    Two landmark studies identified two distinct phosphorylation switches: S147 phosphorylation controls homodimer/heterodimer balance to toggle between motor neuron and OLP fates, while triple serine (S10/S13/S14) phosphorylation maintains promitotic anti-neural functions, revealing how post-translational modifications decode OLIG2's multivalent functions.

    Evidence S147A mutagenesis with transgenic mice and chick electroporation, co-IP for dimer partners; TSM phosphomutant analysis in vivo and in glioma cells

    PMID:21382551 PMID:21382552

    Open questions at the time
    • Kinase(s) for S147 not identified
    • Whether TSM and S147 phosphorylation are coordinated unknown
  10. 2014 High

    Chromatin fractionation and proximity ligation assays showed that TSM phosphorylation directs OLIG2 to active chromatin compartments where it opposes p53 function, while genome-wide ChIP-seq placed OLIG2 at the core of the neural stem cell gene regulatory network, simultaneously activating proliferation genes and repressing differentiation genes.

    Evidence Chromatin fractionation, proximity ligation assay with phosphomutants; ChIP-seq, DNase-seq, histone modification analysis in NS cells

    PMID:24948806 PMID:25294244

    Open questions at the time
    • Direct OLIG2–p53 protein interaction not demonstrated
    • Genome-wide targets in non-glioma progenitors not fully validated functionally
  11. 2017 High

    Reconstitution of the sequential GSK3β→CK2→CDK1/2 kinase cascade that phosphorylates the triple serine motif identified the upstream enzymes and an 'acid blob' mechanism of charge accumulation, providing druggable targets for glioma therapy.

    Evidence In vitro kinase assays, mass spectrometry, kinase inhibitor studies in murine glioma model

    PMID:28355568

    Open questions at the time
    • Phosphatase(s) responsible for TSM dephosphorylation unknown
    • Whether the acid blob modulates specific protein–protein interactions beyond chromatin localization is untested
  12. 2020 High

    Identification of TCF4 as the preferred bHLH heterodimer partner in oligodendrocytes and demonstration that this interaction drives terminal differentiation and myelination resolved the identity of the key OLIG2 partner for the oligodendrocyte lineage specifically.

    Evidence Reciprocal co-IP, Tcf4 conditional KO mice, organotypic slice culture, myelin gene enhancer assays

    PMID:32266943

    Open questions at the time
    • Whether TCF4–OLIG2 heterodimers depend on S147 dephosphorylation not tested
    • Genome-wide binding profile of the heterodimer not determined
  13. 2020 High

    Discovery that SUMO1 conjugation at K27/K76/K112 cooperates with TSM phosphorylation to suppress p53-mediated apoptosis by enhancing OLIG2 chromatin occupancy and occluding p53 from the Cdkn1a promoter linked two post-translational modifications into a unified anti-apoptotic mechanism.

    Evidence SUMOylation site mutagenesis, co-IP, ChIP for p53 at Cdkn1a, temozolomide viability assays

    PMID:32483381

    Open questions at the time
    • SUMO E3 ligase for OLIG2 not identified
    • Whether SUMOylation affects dimerization preference unknown
  14. 2022 High

    Multiple studies resolved downstream effector mechanisms: OLIG2 recruits SETDB1 to deposit H3K9me3 on Sox11 to promote OPC-to-OL differentiation; OLIG2 stabilizes Ddx20 protein to maintain progenitor proliferation via p53 suppression; and Olig2 is essential for immature OL maturation and remyelination, correcting earlier conflicting reports.

    Evidence OLIG2–SETDB1 co-IP, ChIP for H3K9me3 on Sox11, Setdb1 and Sox11 KO/rescue; Olig2–Ddx20 co-IP, Ddx20 conditional KO, Mdm2 splicing analysis; multiple conditional Olig2 KO lines with ChIP-seq and lysolecithin demyelination

    PMID:34974536 PMID:35301318 PMID:36198499

    Open questions at the time
    • Full repertoire of OLIG2-recruited chromatin modifiers unknown
    • Structural basis of OLIG2–SETDB1 or OLIG2–Ddx20 interactions undetermined
    • Whether Ddx20 stabilization is direct or indirect not fully resolved
  15. 2019 High

    OLIG2 triplication in Down syndrome was shown to directly drive interneuron overproduction, with knockdown rescuing molecular, cellular, and behavioral deficits in human organoid and chimeric mouse models, establishing a causal gene-dosage–phenotype link.

    Evidence hiPSC-derived cerebral organoids, DS chimeric mouse models, shRNA knockdown, behavioral testing, single-cell analysis

    PMID:20639873 PMID:31130512

    Open questions at the time
    • Specific OLIG2 target genes driving excess interneuron production not identified
    • Contribution of OLIG1 vs. OLIG2 triplication not fully separated

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the identity of the S147 kinase, the SUMO E3 ligase for OLIG2, the structural basis for phosphorylation-dependent dimer switching, and how OLIG2 coordinates its chromatin-modifying partners across the full spectrum of neural cell fates.
  • S147 kinase identity unknown
  • SUMO E3 ligase unknown
  • No structural model of phospho-dependent homodimer–heterodimer switch
  • Comprehensive chromatin modifier interactome not mapped

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 7 GO:0003677 DNA binding 4
Localization
GO:0005634 nucleus 4 GO:0005694 chromosome 2
Pathway
R-HSA-74160 Gene expression (Transcription) 6 R-HSA-1266738 Developmental Biology 5 R-HSA-1640170 Cell Cycle 5 R-HSA-162582 Signal Transduction 4 R-HSA-4839726 Chromatin organization 2 R-HSA-5357801 Programmed Cell Death 2
Partners
DDX20NEUROG2NKX2.2SETDB1TCF4TP53ZFP488

Evidence

Reading pass · 38 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 OLIG2 (and OLIG1) are required in the pMN domain of the spinal cord for sequential generation of motoneurons and oligodendrocytes; double knockout mice show elimination of motoneurons and abolishment of oligodendrocyte differentiation, with pMN progenitors converting to V2 interneurons and then astrocytes, establishing OLIG2 as a lineage-restricted fate determinant coupling neuronal and glial subtype specification. Genetic loss-of-function (Olig1/2 double-mutant mice) with lineage tracing and cell-type marker analysis Cell High 11955447
2001 OLIG2 functions as a transcriptional repressor; coexpression of OLIG2 with NKX2.2 promotes ectopic and precocious oligodendrocyte differentiation in spinal cord, while OLIG2 alone derepresses Neurogenins and promotes motoneuron differentiation; this dual action depends on spatiotemporal changes in co-expressed transcription factors. In ovo gain-of-function misexpression in chick spinal cord; transcriptional repressor assay Neuron High 11567617
2002 Olig2 alone is essential for motoneuron and oligodendrocyte development in the spinal cord; Olig2-null neuroepithelial cells in the ventral spinal cord fail to differentiate into motoneurons or oligodendrocytes and instead express the astrocyte marker S100β at the time of oligodendrogenesis. Homozygous Olig2 knockout mouse generation; immunohistochemistry for lineage markers Current biology : CB High 12121626
2002 In zebrafish, olig2 is expressed in neural plate cells that give rise to primary motor neurons and oligodendrocytes; loss of olig2 function prevents primary motor neuron and oligodendrocyte development, and overexpression promotes excess formation of both cell types. Hedgehog signaling is required upstream of olig2 expression for oligodendrocyte development. Morpholino loss-of-function, overexpression in zebrafish; genetic epistasis with Hedgehog pathway mutants Developmental biology High 12167410
2003 OLIG2 protein physically interacts with NKX2.2 protein to form a specific complex in mammalian cells and in yeast two-hybrid assay; this interaction is specific (OLIG2 does not bind NKX6.1; NKX2.2 does not interact with NeuroD). Deletion mapping shows the physical complex is insufficient alone for induction of oligodendrocyte progenitors but may underlie the cross-repressive interaction establishing the pMN-p3 boundary. Co-immunoprecipitation in mammalian cells, yeast two-hybrid, deletion mapping The Journal of neuroscience : the official journal of the Society for Neuroscience High 14573534
2004 OLIG2 inhibits astrocytic differentiation by abolishing complex formation between the transcriptional coactivator p300 and STAT3 (activated by LIF/astrocytic differentiation-inducing cytokines), thereby suppressing GFAP promoter activation. OLIG2 protein is lost from nuclei of neural precursor cells during LIF-induced astrocytic differentiation. Co-immunoprecipitation (p300-STAT3 complex), luciferase promoter assay (GFAP promoter), forced expression and knockdown in telencephalic neuroepithelial cells Cell death and differentiation High 14576772
2006 OLIG2 overexpression in embryonic chick spinal cord is sufficient to induce Sox10 and NKX2.2 expression and precocious oligodendrocyte differentiation; genetic evidence places Sox10 downstream of Olig2, but Sox10 can also modulate Olig2 expression (reciprocal regulation). Oligodendrocyte differentiation controlled by Olig2, Sox10 and NKX2.2 is dosage-dependent. In ovo misexpression in chick spinal cord; genetic epistasis; loss-of-function analysis Developmental biology High 17098222
2006 Zfp488, an oligodendrocyte-specific zinc-finger transcription regulator, physically interacts with OLIG2 and cooperates with it to promote precocious and ectopic oligodendrocyte differentiation in chick neural tube; knockdown of Zfp488 in an oligodendroglial cell line downregulates myelin gene expression. Co-immunoprecipitation (Zfp488-OLIG2 interaction); in ovo misexpression; RNAi knockdown Development (Cambridge, England) Medium 16908628
2007 OLIG2 directly represses p21(WAF1/CIP1) expression in neural progenitors and gliomas, and this repression is required for proliferation of normal and tumorigenic CNS stem cells; Olig2 function is required for glioma formation in a genetically defined murine model. Conditional Olig2 knockout in murine glioma model; ChIP and promoter reporter assays for p21 repression Neuron High 17296553
2007 Antagonizing OLIG2 function in the injured cerebral cortex via injection of a dominant-negative form (Olig2VP16) results in significant neurogenesis from infected cells, identifying OLIG2 as a repressor of neurogenesis in cells reacting to brain injury. Retroviral dominant-negative OLIG2 injection in stab-wounded cortex; immunohistochemistry for neuronal markers Proceedings of the National Academy of Sciences of the United States of America Medium 16330768
2007 After brain injury, OLIG2 undergoes nucleocytoplasmic translocation in glial progenitors, and this translocation mediates their differentiation into astrocytes. BMP/Notch-1 signaling promotes this translocation; inhibition of Notch-1 with the γ-secretase inhibitor DAPT blocks Olig2 translocation and glial differentiation in vitro. Immunofluorescence localization of Olig2 after stab wound in rats; in vitro BMP/serum treatment; DAPT pharmacological inhibition Journal of neuroscience research Medium 17510983
2007 Olig2 is required for white matter astrocyte development; conditional Olig2 ablation in a spatiotemporally controlled manner severely compromises formation of astrocytes in white matter of cortex and spinal cord; postnatal Olig2 function is specifically required for astrocyte differentiation in cerebral white matter. Conditional (spatiotemporally controlled) Olig2 knockout mouse; cell-type-specific mutagenesis; fate mapping Development (Cambridge, England) High 17428828
2008 Olig2 is upregulated in reactive astrocytes after cortical injury, coinciding with their proliferation. Olig2 ablation in GFAP+ astrocytes (not in oligodendroglial or neuronal lineages) decreases proliferation of reactive astrocytes in response to injury, establishing Olig2 as critical for post-injury gliosis. Cell-type-specific Olig2 conditional mutagenesis; lineage-restricted transgenic reporter lines; BrdU proliferation assay The Journal of neuroscience : the official journal of the Society for Neuroscience High 18945906
2011 Serine 147 (S147) in the helix-loop-helix domain of OLIG2 is phosphorylated during motor neuron (MN) production and dephosphorylated at the onset of oligodendrocyte precursor genesis. S147A mutation abolishes MN production without preventing OLP production. Phosphorylated OLIG2 forms stable homodimers; unphosphorylated OLIG2(S147A) preferentially forms heterodimers with Neurogenin 2 or other bHLH partners, providing a molecular basis for the MN-OLP fate switch. Site-directed mutagenesis (S147A), transgenic mice, chick in ovo electroporation, P19 cell culture; co-immunoprecipitation for dimer partners Neuron High 21382552
2011 A conserved triple serine motif (S10, S13, S14) in the amino-terminal domain of OLIG2 is phosphorylated in a developmentally regulated manner; phosphorylation of this motif maintains antineural (promitotic) functions in multipotent CNS progenitor cells and in human glioma cells. Unphosphorylated OLIG2 loses this mitogenic activity. Phosphorylation site mapping, mutagenesis, in vivo mouse studies, human glioma cell analysis Neuron High 21382551
2013 Notch/RBP-J signaling regulates nucleocytoplasmic Olig2 translocation in reactive astrocytes after ischemic stroke; DAPT (γ-secretase inhibitor) inhibits nuclear translocation of Olig2, reduces reactive astrocyte proliferation and differentiation, linking Notch signaling to Olig2 nuclear localization. Notch reporter mice; BrdU labeling; DAPT pharmacological inhibition; immunofluorescence localization Neuroscience research Medium 23396245
2013 Stage-specific deletion of Olig2 in oligodendrocyte precursor cells (OPCs) inhibits differentiation and causes hypomyelination, but deletion in immature OLs was reported to enhance maturation (though a later study disputes this). Deletion of Olig2 in OPCs reduces Olig1 expression, while deletion in immature OLs increases Olig1 approximately threefold; enforced Olig1 expression in OPCs rescues the differentiation phenotype of Olig2-null OPCs. Stage-specific conditional Olig2 KO (CNPase-Cre and PLP-CreERT); rescue by Olig1 overexpression in null background; in vitro and in vivo myelination analysis The Journal of neuroscience : the official journal of the Society for Neuroscience Medium 23658182
2014 Phosphorylation of the triple serine motif (S10, S13, S14) regulates intranuclear compartmentalization of OLIG2: phosphorylated OLIG2 localizes to transcriptionally active open chromatin together with coregulator proteins, while unphosphorylated OLIG2 localizes to transcriptionally inactive condensed chromatin. Proximity ligation assays show phosphorylated OLIG2 comes within 30 nm of p53 in the open chromatin compartment, revealing an oppositional relationship with p53 that underlies promitogenic functions. Chromatin fractionation, proximity ligation assay, phosphomutant analysis, co-immunoprecipitation The Journal of neuroscience : the official journal of the Society for Neuroscience High 24948806
2014 OLIG2 is identified as a multifunctional regulator of neural stem cell self-renewal; ChIP-seq shows OLIG2 concurrently activates pro-proliferation genes and prevents premature activation of neuronal differentiation genes; DNase-seq and chromatin analysis reveal OLIG2 at the core of the neural stem cell gene regulatory network. ChIP-seq, DNase-seq, histone modification analysis, machine learning, functional KD validation in NS cells Genome research High 25294244
2016 Unphosphorylated OLIG2 (at S10, S13, S14) induces TGF-β2 expression and promotes invasive mesenchymal properties in glioma cells both in vitro and in vivo; phosphomimetic OLIG2 blocks TGF-β2-mediated invasion and reduces expression of invasion genes ZEB1 and CD44. Inhibition of the TGF-β2 pathway blocks OLIG2-dependent invasion. Phosphomutant expression (unphosphorylatable vs. phosphomimetic), TGF-β2 pathway inhibition, in vitro migration/invasion assays, in vivo xenograft models Cell reports High 27396340
2016 OLIG2 modulates growth factor signaling in glioma stem-like cells (GSCs); a positive feedforward loop exists between OLIG2 and EGFR; loss of OLIG2 function results in mesenchymal transformation in PDGFRα-HIGH GSCs; OLIG2 regulates EGFR expression in a context-dependent manner. Biochemical analysis (western blot, co-expression), loss-of-function (shRNA knockdown), comparison of EGFR-HIGH vs. PDGFRα-HIGH GSC populations Cell reports Medium 27626655
2016 Olig2 transcriptionally targets Gpr17 locus (identified by ChIP-seq genomic occupancy analysis); after oligodendrocyte injury, Olig2 is upregulated and activates Gpr17 transcription; Gpr17 inhibits oligodendrocyte survival by reducing intracellular cAMP and inducing pro-apoptotic gene Xaf1; loss of Gpr17 leads to earlier remyelination onset. ChIP-seq (chromatin immunoprecipitation sequencing) after lysolecithin injury; Gpr17 global and oligodendrocyte-specific KO mice; cAMP measurements; pharmacological inhibition (pranlukast) The Journal of neuroscience : the official journal of the Society for Neuroscience High 27733608
2017 A sequentially priming phosphorylation cascade of GSK3α/β, CK2, and CDK1/2 is collectively necessary and sufficient to phosphorylate the triple serine motif (S10, S13, S14) in OLIG2; phosphorylation of the motif itself templates phosphorylation of additional serines, creating a highly charged 'acid blob' in the amino terminus. Small molecule inhibitors of this cascade have anti-glioma activity. In vitro kinase assays, mass spectrometry phosphorylation mapping, kinase inhibitor studies, murine glioma model Cell reports High 28355568
2018 Deletion of Olig2 in NG2 cells of postnatal neocortex causes NG2 cells to switch fate to protoplasmic astrocytes; this fate conversion decreases with age over the first 3 postnatal weeks. Sox10 expression is maintained after Olig2 deletion in older cells despite early NFIA upregulation. Inhibiting cell proliferation reduces astrocyte differentiation from Olig2-deleted perinatal NG2 cells, suggesting cell division facilitates nuclear reorganization for astrocyte fate conversion. Conditional Olig2 KO in NG2 cells (tamoxifen-inducible); fate mapping; slice culture with proliferation inhibitor The Journal of neuroscience : the official journal of the Society for Neuroscience High 29382710
2018 Olig2 represses expression of Notch signaling effectors Hes1 and Hes5 in motor neuron progenitors; repression of Hes5 appears to be direct, via a conserved regulatory element within the Hes5 locus that restricts Hes5 expression from MN progenitors; this coordinates patterning and neuronal differentiation timing. Single-cell transcriptomics with gene expression dynamics reconstruction; identification of conserved Hes5 regulatory element; epistasis analysis PLoS biology Medium 29389974
2019 Increased OLIG2 expression in Down syndrome directly upregulates interneuron lineage-determining transcription factors, leading to overproduction of specific GABAergic interneuron subclasses; shRNA-mediated knockdown of OLIG2 in DS neural progenitors reverses abnormal gene expression, reduces interneuron overproduction in organoids and chimeric mouse brains, and improves behavioral deficits. hiPSC-derived cerebral organoids, DS chimeric mouse models, shRNA knockdown of OLIG2, behavioral testing, single-cell analysis Cell stem cell High 31130512
2020 OLIG2 is conjugated by SUMO1 at three lysine residues (K27, K76, K112); SUMOylation is required for OLIG2 to suppress p53-mediated cell cycle arrest and apoptosis in response to genotoxic damage, and to enhance temozolomide resistance in glioma. Both SUMOylation and triple serine motif (TSM) phosphorylation are required for this antiapoptotic function; SUMOylation enhances OLIG2 chromatin-targeting ability, occluding p53 recruitment to the Cdkn1a promoter. SUMOylation site mutagenesis (K27, K76, K112R), co-immunoprecipitation, ChIP (p53 recruitment to Cdkn1a promoter), cell viability assays with TMZ, apoptosis assays Cell death and differentiation High 32483381
2020 TCF4 is the preferred heterodimerization partner of OLIG2 in oligodendrocytes; this physical interaction is required for terminal oligodendrocyte differentiation and myelination in a cell-autonomous manner. Genetic studies in mouse and functional enhancer studies on myelin genes confirm relevance of the OLIG2-TCF4 interaction. Co-immunoprecipitation (OLIG2-TCF4 interaction), mouse conditional KO (Tcf4), organotypic slice culture, primary cell cultures, myelin gene enhancer assays Nucleic acids research High 32266943
2022 OLIG2 recruits the tri-methyltransferase SETDB1 to mediate H3K9me3 modification on the Sox11 gene, leading to transcriptional repression of Sox11 during OPC-to-immature oligodendrocyte differentiation; tissue-specific Setdb1 deletion causes hypomyelination and remyelination defects; Sox11 knockdown or depletion rescues hypomyelination caused by Olig2 loss. Co-immunoprecipitation (OLIG2-SETDB1), ChIP (H3K9me3 on Sox11 locus), tissue-specific Setdb1 KO mice, Sox11 siRNA/KO rescue experiments Nature communications High 35301318
2022 Olig2 is essential for immature oligodendrocyte maturation and remyelination; analysis using multiple immature OL-expressing Cre lines (Plp1, Mobp, Mog promoters) shows Olig2 deletion in immature OLs causes defects in maturation and myelination, not enhancement. Genomic occupancy analysis reveals Olig2 targets enhancers of key myelination-related genes. Olig2 is not required for myelin maintenance in mature OLs but is critical for remyelination after lysolecithin injury. Multiple conditional Olig2 KO lines (Plp1-Cre, Mobp-Cre, Mog-Cre), ChIP-seq genomic occupancy, lysolecithin demyelination model, lineage tracing The Journal of neuroscience : the official journal of the Society for Neuroscience High 36198499
2022 Ddx20 (DEAD-box helicase 20) is a novel Olig2-binding protein; Olig2 contributes to NPC proliferation through Ddx20 protein stabilization. CNS-specific Ddx20 conditional KO causes apoptosis and cell cycle arrest in NPCs and OPCs through potentiation of p53 pathway in both DNA damage-dependent and independent manners, including SMN complex disruption and abnormal Mdm2 mRNA splicing. Co-immunoprecipitation (Olig2-Ddx20), Ddx20 conditional KO mice, Olig2-null NPC analysis, western blot for Ddx20 stability, splicing analysis of Mdm2 Cell death and differentiation High 34974536
2014 Prox1, a transcription repressor, directly binds to the proximal promoter and K23 enhancer of the Olig2 gene locus (by ChIP analysis in mouse neural tube), suppresses Olig2 transcription, and controls MN versus V2 interneuron identity in ventral spinal cord. ChIP in mouse neural tube, plasmid-based transcriptional assays, gain- and loss-of-function in mouse NPCs and chick neural tube The Journal of neuroscience : the official journal of the Society for Neuroscience Medium 25411508
2006 OLIG2 suppresses proliferation of glioma cells by transactivating p27Kip1; luciferase and EMSA assays show OLIG2-dependent activation through the CTF site of the p27Kip1 promoter; siRNA against p27Kip1 rescues OLIG2-mediated growth inhibition, demonstrating that OLIG2's antiproliferative effect is mediated through p27Kip1. Tet-off inducible OLIG2 expression system; luciferase reporter assay (p27Kip1 promoter); EMSA; siRNA rescue Journal of cell science Medium 16554441
2009 In zebrafish, olig2 regulates Sim1 expression; olig2 and sim1 are co-expressed in a subset of diencephalic progenitors; loss of either olig2 or sim1 impairs dopaminergic neuron development; olig2 acts upstream of sim1, and gain of sim1 function rescues dopaminergic differentiation deficits caused by olig2 knockdown. Morpholino knockdown in zebrafish; in situ hybridization; epistasis rescue experiment Developmental dynamics : an official publication of the American Association of Anatomists Medium 19253397
2008 FGF2 promotes Olig2 upregulation and OPC generation from embryonic dorsal spinal cord NPCs by counteracting BMP signaling at the Smad1 level (via MAPK pathway); SMAD4 associates with a Smad binding site in the Olig2 promoter in undifferentiated cells and dissociates upon differentiation, indicating Smad-containing complexes directly regulate Olig2 transcription. ChIP (SMAD4 on Olig2 promoter), MAPK and BMP pathway inhibition, nuclear localization assays for C-term-pSMAD1, FGF2 treatment of dorsal spinal cord NPCs PloS one Medium 18682850
2000 OLIG2 (originally designated BHLHB1) inhibits E2A-mediated transcriptional activation when expressed ectopically in NIH 3T3 fibroblasts and Jurkat T cells; expression is normally restricted to neural tissues but activated in T-cell leukemia by chromosomal translocation placing the TCR-alpha enhancer near the BHLHB1 locus. Transcriptional reporter assays in fibroblasts and T cells; cloning of chromosomal translocation breakpoints Proceedings of the National Academy of Sciences of the United States of America Medium 10737801
2016 BRG1 (Brg1), the SWI/SNF chromatin remodeling complex subunit, interacts with the proximal Olig2 promoter and represses Olig2 transcription in E14 mouse cortex; Brg1-null NPCs show precocious Olig2 expression but fail to differentiate into OPCs, indicating Brg1 is required both for repression of Olig2 and for subsequent OPC differentiation. ChIP (Brg1 on Olig2 promoter), Brg1 conditional KO mice, immunohistochemistry for OPC markers Developmental biology Medium 27067865
2010 Olig1 and Olig2 are overexpressed in the Ts65Dn (Down syndrome model) forebrain; genetic normalization of Olig1 and Olig2 dosage rescues the inhibitory neuron imbalance phenotype (increased GABAergic interneurons) in the Ts65Dn brain, directly linking triplication of these genes to neurodevelopmental abnormalities. Genetic rescue by dosage normalization of Olig1/Olig2 in Ts65Dn mice; immunohistochemistry; electrophysiology Nature neuroscience High 20639873

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 The bHLH transcription factors OLIG2 and OLIG1 couple neuronal and glial subtype specification. Cell 847 11955447
2001 The bHLH transcription factor Olig2 promotes oligodendrocyte differentiation in collaboration with Nkx2.2. Neuron 478 11567617
2008 Progeny of Olig2-expressing progenitors in the gray and white matter of the adult mouse cerebral cortex. The Journal of neuroscience : the official journal of the Society for Neuroscience 426 18842903
2002 The basic helix-loop-helix factor olig2 is essential for the development of motoneuron and oligodendrocyte lineages. Current biology : CB 415 12121626
2007 Olig2-regulated lineage-restricted pathway controls replication competence in neural stem cells and malignant glioma. Neuron 412 17296553
2004 The oligodendroglial lineage marker OLIG2 is universally expressed in diffuse gliomas. Journal of neuropathology and experimental neurology 345 15198128
2005 Expression pattern of the transcription factor Olig2 in response to brain injuries: implications for neuronal repair. Proceedings of the National Academy of Sciences of the United States of America 322 16330768
2002 olig2 is required for zebrafish primary motor neuron and oligodendrocyte development. Developmental biology 252 12167410
2004 Increased expression of Nkx2.2 and Olig2 identifies reactive oligodendrocyte progenitor cells responding to demyelination in the adult CNS. Molecular and cellular neurosciences 244 15519240
2004 Regionalization and fate specification in neurospheres: the role of Olig2 and Pax6. Molecular and cellular neurosciences 226 15080895
2003 Neural cell fate analysis in zebrafish using olig2 BAC transgenics. Methods in cell science : an official journal of the Society for In Vitro Biology 225 14739582
2005 Olig2 directs astrocyte and oligodendrocyte formation in postnatal subventricular zone cells. The Journal of neuroscience : the official journal of the Society for Neuroscience 208 16093378
2010 Olig1 and Olig2 triplication causes developmental brain defects in Down syndrome. Nature neuroscience 179 20639873
2002 Dual origin of spinal oligodendrocyte progenitors and evidence for the cooperative role of Olig2 and Nkx2.2 in the control of oligodendrocyte differentiation. Development (Cambridge, England) 177 11830569
2007 A crucial role for Olig2 in white matter astrocyte development. Development (Cambridge, England) 164 17428828
2006 Induction of oligodendrocyte differentiation by Olig2 and Sox10: evidence for reciprocal interactions and dosage-dependent mechanisms. Developmental biology 159 17098222
2019 OLIG2 Drives Abnormal Neurodevelopmental Phenotypes in Human iPSC-Based Organoid and Chimeric Mouse Models of Down Syndrome. Cell stem cell 151 31130512
2006 Olig2-positive progenitors in the embryonic spinal cord give rise not only to motoneurons and oligodendrocytes, but also to a subset of astrocytes and ependymal cells. Developmental biology 148 16581057
2015 Gain of Olig2 function in oligodendrocyte progenitors promotes remyelination. Brain : a journal of neurology 131 25564492
2004 Anti-human Olig2 antibody as a useful immunohistochemical marker of normal oligodendrocytes and gliomas. The American journal of pathology 123 15111318
2009 NG2+/Olig2+ cells are the major cycle-related cell population of the adult human normal brain. Brain pathology (Zurich, Switzerland) 119 19486010
2012 Transcription factor Olig2 defines subpopulations of retinal progenitor cells biased toward specific cell fates. Proceedings of the National Academy of Sciences of the United States of America 110 22543161
2011 Phosphorylation regulates OLIG2 cofactor choice and the motor neuron-oligodendrocyte fate switch. Neuron 109 21382552
2011 Phosphorylation state of Olig2 regulates proliferation of neural progenitors. Neuron 103 21382551
2006 An oligodendrocyte-specific zinc-finger transcription regulator cooperates with Olig2 to promote oligodendrocyte differentiation. Development (Cambridge, England) 101 16908628
2006 Convergent evidence that oligodendrocyte lineage transcription factor 2 (OLIG2) and interacting genes influence susceptibility to schizophrenia. Proceedings of the National Academy of Sciences of the United States of America 100 16891421
2008 Genetic fate mapping of Olig2 progenitors in the injured adult cerebral cortex reveals preferential differentiation into astrocytes. Journal of neuroscience research 98 18816798
2013 Stage-specific deletion of Olig2 conveys opposing functions on differentiation and maturation of oligodendrocytes. The Journal of neuroscience : the official journal of the Society for Neuroscience 95 23658182
2008 The basic helix-loop-helix transcription factor olig2 is critical for reactive astrocyte proliferation after cortical injury. The Journal of neuroscience : the official journal of the Society for Neuroscience 95 18945906
2004 Negative regulatory effect of an oligodendrocytic bHLH factor OLIG2 on the astrocytic differentiation pathway. Cell death and differentiation 85 14576772
1992 Oligo(2'-O-methyl)ribonucleotides. Effective probes for duplex DNA. FEBS letters 83 1633847
2007 An olig2 reporter gene marks oligodendrocyte precursors in the postembryonic spinal cord of zebrafish. Developmental dynamics : an official publication of the American Association of Anatomists 82 17969181
2012 TricycloDNA-modified oligo-2'-deoxyribonucleotides reduce scavenger receptor B1 mRNA in hepatic and extra-hepatic tissues--a comparative study of oligonucleotide length, design and chemistry. Nucleic acids research 78 22467214
2016 Olig2-Targeted G-Protein-Coupled Receptor Gpr17 Regulates Oligodendrocyte Survival in Response to Lysolecithin-Induced Demyelination. The Journal of neuroscience : the official journal of the Society for Neuroscience 77 27733608
2007 A genetic family-based association study of OLIG2 in obsessive-compulsive disorder. Archives of general psychiatry 75 17283288
2007 Evidence that nucleocytoplasmic Olig2 translocation mediates brain-injury-induced differentiation of glial precursors to astrocytes. Journal of neuroscience research 72 17510983
2003 Expression of the oligodendroglial lineage-associated markers Olig1 and Olig2 in different types of human gliomas. Journal of neuropathology and experimental neurology 72 14575240
2006 Involvement of the Olig2 transcription factor in cholinergic neuron development of the basal forebrain. Developmental biology 71 16537079
2021 Using the lineage determinants Olig2 and Sox10 to explore transcriptional regulation of oligodendrocyte development. Developmental neurobiology 70 34480425
2013 hESC-derived Olig2+ progenitors generate a subtype of astroglia with protective effects against ischaemic brain injury. Nature communications 68 23880652
2022 The Oligodendrocyte Transcription Factor 2 OLIG2 regulates transcriptional repression during myelinogenesis in rodents. Nature communications 67 35301318
2009 Olig2+ precursors produce abducens motor neurons and oligodendrocytes in the zebrafish hindbrain. The Journal of neuroscience : the official journal of the Society for Neuroscience 64 19244509
2018 Olig2 and Hes regulatory dynamics during motor neuron differentiation revealed by single cell transcriptomics. PLoS biology 63 29389974
2000 The t(14;21)(q11.2;q22) chromosomal translocation associated with T-cell acute lymphoblastic leukemia activates the BHLHB1 gene. Proceedings of the National Academy of Sciences of the United States of America 63 10737801
2010 OLIG2 is differentially expressed in pediatric astrocytic and in ependymal neoplasms. Journal of neuro-oncology 57 21193945
2005 Olig2 expression, GFAP, p53 and 1p loss analysis contribute to glioma subclassification. Neuropathology and applied neurobiology 57 15634232
2002 Non-overlapping expression of Olig3 and Olig2 in the embryonic neural tube. Mechanisms of development 56 11960707
2003 Cross-repressive interaction of the Olig2 and Nkx2.2 transcription factors in developing neural tube associated with formation of a specific physical complex. The Journal of neuroscience : the official journal of the Society for Neuroscience 55 14573534
2016 Post-translational Modifications of OLIG2 Regulate Glioma Invasion through the TGF-β Pathway. Cell reports 54 27396340
2010 Modulation of fate determinants Olig2 and Pax6 in resident glia evokes spiking neuroblasts in a model of mild brain ischemia. Stroke 52 21051674
2008 Induction of Olig2 precursors by FGF involves BMP signalling blockade at the Smad level. PloS one 51 18682850
2014 Characterization of the neural stem cell gene regulatory network identifies OLIG2 as a multifunctional regulator of self-renewal. Genome research 50 25294244
1996 Oligo-2'-fluoro-2'-deoxynucleotide N3'-->P5' phosphoramidates: synthesis and properties. Nucleic acids research 49 8760881
2021 Region-specific distribution of Olig2-expressing astrocytes in adult mouse brain and spinal cord. Molecular brain 48 33618751
2020 Transcription factor Tcf4 is the preferred heterodimerization partner for Olig2 in oligodendrocytes and required for differentiation. Nucleic acids research 48 32266943
2016 Lineage-Restricted OLIG2-RTK Signaling Governs the Molecular Subtype of Glioma Stem-like Cells. Cell reports 47 27626655
2008 Hh and Wnt signaling regulate formation of olig2+ neurons in the zebrafish cerebellum. Developmental biology 47 18423594
2014 Identification of OLIG2 as the most specific glioblastoma stem cell marker starting from comparative analysis of data from similar DNA chip microarray platforms. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 41 25384509
2009 Quantitative analysis of mitotic Olig2 cells in adult human brain and gliomas: implications for glioma histogenesis and biology. Glia 41 18837053
2013 Notch signaling regulates nucleocytoplasmic Olig2 translocation in reactive astrocytes differentiation after ischemic stroke. Neuroscience research 40 23396245
2006 Induced expression of Olig2 is sufficient for oligodendrocyte specification but not for motoneuron specification and astrocyte repression. Molecular and cellular neurosciences 40 17035043
2017 Harnessing OLIG2 function in tumorigenicity and plasticity to target malignant gliomas. Cell cycle (Georgetown, Tex.) 39 28806136
2016 Distinct cortical and sub-cortical neurogenic domains for GABAergic interneuron precursor transcription factors NKX2.1, OLIG2 and COUP-TFII in early fetal human telencephalon. Brain structure & function 39 27905023
2013 Sonic hedgehog promotes generation and maintenance of human forebrain Olig2 progenitors. Frontiers in cellular neuroscience 39 24379757
2012 Effects of Olig2-overexpressing neural stem cells and myelin basic protein-activated T cells on recovery from spinal cord injury. Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics 39 22173726
2016 Brg1 directly regulates Olig2 transcription and is required for oligodendrocyte progenitor cell specification. Developmental biology 36 27067865
2007 OLIG2 is a useful immunohistochemical marker in differential diagnosis of clear cell primary CNS neoplasms. Histopathology 36 17257132
2010 Expression of the transcription factor Olig2 in proliferating cells in the adult zebrafish telencephalon. Developmental dynamics : an official publication of the American Association of Anatomists 34 20981834
2021 One-step Reprogramming of Human Fibroblasts into Oligodendrocyte-like Cells by SOX10, OLIG2, and NKX6.2. Stem cell reports 32 33770499
2017 The transcription factor Olig2 is important for the biology of diffuse intrinsic pontine gliomas. Neuro-oncology 32 28339768
2022 Shh and Olig2 sequentially regulate oligodendrocyte differentiation from hiPSCs for the treatment of ischemic stroke. Theranostics 31 35547747
2009 Neural protein Olig2 acts upstream of the transcriptional regulator Sim1 to specify diencephalic dopaminergic neurons. Developmental dynamics : an official publication of the American Association of Anatomists 31 19253397
2020 Olig2 SUMOylation protects against genotoxic damage response by antagonizing p53 gene targeting. Cell death and differentiation 30 32483381
2018 Age-Dependent Decline in Fate Switch from NG2 Cells to Astrocytes After Olig2 Deletion. The Journal of neuroscience : the official journal of the Society for Neuroscience 30 29382710
2017 A Sequentially Priming Phosphorylation Cascade Activates the Gliomagenic Transcription Factor Olig2. Cell reports 30 28355568
2009 Bioluminescence imaging of Olig2-neural stem cells reveals improved engraftment in a demyelination mouse model. Stem cells (Dayton, Ohio) 30 19544465
2015 Human Dental Pulp Stem Cells Differentiate into Oligodendrocyte Progenitors Using the Expression of Olig2 Transcription Factor. Cells, tissues, organs 29 25966902
2007 Differential regulation of basic helix-loop-helix factors Mash1 and Olig2 by beta-amyloid accelerates both differentiation and death of cultured neural stem/progenitor cells. The Journal of biological chemistry 29 17488716
2016 Molecular mechanisms of OLIG2 transcription factor in brain cancer. Oncotarget 27 27447975
2012 Olig2-positive cells in glioneuronal tumors show both glial and neuronal characters: the implication of a common progenitor cell? Neuropathology : official journal of the Japanese Society of Neuropathology 27 23025580
2010 A systematic enhancer screen using lentivector transgenesis identifies conserved and non-conserved functional elements at the Olig1 and Olig2 locus. PloS one 27 21206754
2005 OLIG2 (BHLHB1), a bHLH transcription factor, contributes to leukemogenesis in concert with LMO1. Cancer research 27 16103065
2009 Olig2 transcription factor in the developing and injured forebrain; cell lineage and glial development. Molecules and cells 26 19390819
2016 Olig2 regulates Purkinje cell generation in the early developing mouse cerebellum. Scientific reports 25 27469598
2014 Pten loss in Olig2 expressing neural progenitor cells and oligodendrocytes leads to interneuron dysplasia and leukodystrophy. Stem cells (Dayton, Ohio) 25 24395742
2014 Differentiation of neurosphere-derived rat neural stem cells into oligodendrocyte-like cells by repressing PDGF-α and Olig2 with triiodothyronine. Tissue & cell 25 25200619
2019 OLIG2 is a marker of the fusion protein-driven neurodevelopmental transcriptional signature in alveolar rhabdomyosarcoma. Human pathology 24 31299267
2012 Antagonistic modulation of gliomagenesis by Pax6 and Olig2 in PDGF-induced oligodendroglioma. International journal of cancer 24 22514120
2011 Differential and cooperative actions of Olig1 and Olig2 transcription factors on immature proliferating cells after contusive spinal cord injury. Glia 24 21538562
2024 Transcription factors ASCL1 and OLIG2 drive glioblastoma initiation and co-regulate tumor cell types and migration. Nature communications 23 39609428
2014 An amino terminal phosphorylation motif regulates intranuclear compartmentalization of Olig2 in neural progenitor cells. The Journal of neuroscience : the official journal of the Society for Neuroscience 23 24948806
2014 Prox1 regulates Olig2 expression to modulate binary fate decisions in spinal cord neurons. The Journal of neuroscience : the official journal of the Society for Neuroscience 23 25411508
2004 Analysis of the bHLH transcription factors Olig1 and Olig2 in brain tumors. Journal of neuro-oncology 23 15164981
2022 Olig2 Ablation in Immature Oligodendrocytes Does Not Enhance CNS Myelination and Remyelination. The Journal of neuroscience : the official journal of the Society for Neuroscience 22 36198499
2017 Multiple spatially related pharmacophores define small molecule inhibitors of OLIG2 in glioblastoma. Oncotarget 22 26517684
2011 All the embryo's a stage, and Olig2 in its time plays many parts. Neuron 22 21382543
2006 A novel function of OLIG2 to suppress human glial tumor cell growth via p27Kip1 transactivation. Journal of cell science 22 16554441
2022 Ddx20, an Olig2 binding factor, governs the survival of neural and oligodendrocyte progenitor cells via proper Mdm2 splicing and p53 suppression. Cell death and differentiation 21 34974536
2016 Accelerated generation of oligodendrocyte progenitor cells from human induced pluripotent stem cells by forced expression of Sox10 and Olig2. Science China. Life sciences 21 27785726
2014 Development of the prethalamus is crucial for thalamocortical projection formation and is regulated by Olig2. Development (Cambridge, England) 21 24803655