Affinage

NEUROG2

Neurogenin-2 · UniProt Q9H2A3

Length
272 aa
Mass
28.6 kDa
Annotated
2026-04-29
92 papers in source corpus 26 papers cited in narrative 27 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

NEUROG2 is a proneural basic helix-loop-helix (bHLH) transcription factor that functions as a pioneer factor to open chromatin, demethylate DNA, and reorganize three-dimensional chromatin architecture at neurogenic loci, thereby driving neuronal commitment and subtype specification across multiple CNS and PNS regions (PMID:35132236, PMID:28157484, PMID:31086315). It binds E-box sequences at largely distinct genomic sites compared to Ascl1—determined by intrinsic DNA-binding domain preferences rather than prior chromatin state—and activates targets including NeuroD, Dll3, Tbr2, and RND2 while repressing cyclins (CCND1, CCNE1/2, CCNA2), Olig2, and Isl1 to coordinate cell cycle exit with neuronal differentiation (PMID:31086315, PMID:22547683, PMID:33187539, PMID:36537573). NEUROG2 activity is temporally controlled by CDK-mediated multisite phosphorylation that reduces DNA-binding affinity and differentially tunes target promoter responses, by Fbxo9-mediated and non-canonical cysteine ubiquitylation that promote its rapid turnover, and by MTGR1-dependent negative feedback that blocks the NEUROG2/E47 heterodimer from DNA (PMID:22491944, PMID:32029586, PMID:20807509, PMID:19646530). Upstream, Pax3 directly activates the Neurog2 promoter in a manner gated by SIRT1-regulated Pax3 acetylation, while Notch/Rbpj signaling and ETV5/CoREST repress Neurog2 transcription to balance progenitor maintenance against neuronal differentiation (PMID:18308300, PMID:21169561, PMID:25100656, PMID:31273540).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 2002 High

    Establishing that Neurog2 acts permissively rather than instructively in neuronal subtype specification resolved how two proneural factors with overlapping expression can generate different neuron types — Mash1 instructs identity while Neurog2 enables it.

    Evidence Knock-in replacement of Mash1 and Ngn2 coding sequences in mice with loss-of-function and gain-of-function epistasis

    PMID:11825874

    Open questions at the time
    • Molecular basis for permissive versus instructive activity not identified
    • Cofactors conferring subtype specificity not determined
  2. 2005 High

    Demonstrating that Neurog2 modulates dorsal interneuron populations without being required for any specific type, with Mash1 epistatic, clarified the redundancy hierarchy between proneural factors in the spinal cord.

    Evidence Mash1 and Ngn2 single and double knockout mice with immunohistochemical analysis of interneuron subtypes

    PMID:15901662

    Open questions at the time
    • Compensatory mechanisms between Mash1 and Ngn2 not molecularly dissected
    • Whether redundancy reflects shared or distinct target gene sets was unknown
  3. 2008 High

    Identifying Pax3 as a direct upstream activator of Neurog2 transcription, and Tbr2 as a downstream target suppressed by Notch signaling, anchored Neurog2 within a defined transcriptional cascade linking patterning to neurogenesis.

    Evidence Promoter-luciferase, EMSA, and ChIP for Pax3 at Neurog2 promoter; daughter-cell tracking with gamma-secretase inhibition for Notch–Neurog2–Tbr2 axis

    PMID:18308300 PMID:19059340

    Open questions at the time
    • Tbr2 as direct Neurog2 target lacked ChIP validation at this time
    • Other Pax family members' contributions to Neurog2 regulation not tested
  4. 2009 High

    Three discoveries collectively defined how Neurog2 activity is terminated and diversified: MTGR1 forms a negative feedback loop by blocking NEUROG2/E47 DNA binding; Ptf1a/Rbpj directly activates a Neurog2 3' enhancer in dorsal neural tube; and Neurog2 regulates Dll3 through specific E-box elements, revealing heterodimer-dependent promoter selectivity.

    Evidence Co-IP, DNA-binding assays, and in vivo spinal cord analysis for MTGR1; enhancer-reporter transgenics and ChIP for Ptf1a; E-box mutagenesis and EMSA for Dll3 promoter

    PMID:19389376 PMID:19641016 PMID:19646530

    Open questions at the time
    • Whether MTGR1 feedback is required in vivo for neurogenesis timing not shown by conditional loss-of-function
    • Structural basis of Neurog2/E47 versus Ascl1 homodimer E-box selectivity unknown
  5. 2010 High

    Multiple studies in 2010 revealed layered regulation of Neurog2 at every level: Pax3 acetylation/SIRT1 tunes Neurog2 transcription; H3K27 methylation/KDM6B modulates epigenetic access; non-canonical cysteine ubiquitylation drives rapid Neurog2 protein turnover; and Neurog2 initiates retinal neurogenesis with Ascl1 providing compensatory rescue.

    Evidence Pax3 mutagenesis and SIRT1 ChIP/KD/OE; ChIP for H3K27me2 and KDM6B at Neurog2 promoter; cysteine mutagenesis and ubiquitylation assays in Xenopus/P19 cells; Neurog2 null retinal phenotype with Ascl1 epistasis

    PMID:20144606 PMID:20214951 PMID:20807509 PMID:20833714 PMID:21169561

    Open questions at the time
    • Identity of the E3 ligase for cysteine ubiquitylation not determined at this point
    • Whether KDM6B directly targets Neurog2 locus or acts indirectly not resolved
    • Physiological significance of cysteine versus lysine ubiquitylation in vivo unknown
  6. 2012 High

    Showing that CDK-dependent multisite phosphorylation of Neurog2 differentially regulates distinct target promoters — NeuroD being phospho-sensitive and Delta resistant — explained how a single factor's phosphorylation state can uncouple differentiation from lateral inhibition signaling.

    Evidence Phospho-mutant Ngn2 constructs tested by promoter reporters in Xenopus embryos and P19 cells

    PMID:22491944

    Open questions at the time
    • In vivo phospho-site mutant knock-in not performed
    • Kinase identity beyond generic CDK not specified
    • How phosphorylation interacts with ubiquitylation-based turnover not addressed
  7. 2012 High

    Demonstrating that NEUROG2 represses G1/S cyclins (CCND1, CCNE1/2, CCNA2) to enforce cell cycle exit independently of neuronal differentiation resolved the long-standing question of whether proneural factors couple or separately control these two processes.

    Evidence Gain-of-function with NEUROG2-VP16 and NEUROG2-EnR in chicken embryos; gene expression profiling and S-phase entry assays

    PMID:22547683

    Open questions at the time
    • Direct versus indirect mechanism of cyclin repression not fully resolved
    • Whether cyclin repression requires specific cofactors not tested
  8. 2014 High

    Systematic genetic dissection of Notch pathway components showed that Notch1/Notch3/Rbpj, but not Hes1/3/5, repress Neurog2 in the retina, distinguishing its regulation from that of Atoh7 and revealing non-canonical Notch effectors.

    Evidence Compound mutant mice for Notch1, Notch3, Rbpj, and Hes1/3/5 with immunostaining and epistasis in retina

    PMID:25100656

    Open questions at the time
    • Identity of the Rbpj-dependent but Hes-independent repressor of Neurog2 not identified
    • Whether this non-Hes mechanism operates outside the retina unknown
  9. 2016 High

    Establishing NEUROG2 as a pioneer transcription factor that opens chromatin de novo during fibroblast-to-neuron reprogramming provided the first direct evidence that its neurogenic activity involves remodeling of closed chromatin, with SOX4 and CREB1 as critical downstream effectors.

    Evidence ATAC-seq, H3K27ac ChIP-seq, RNA-seq, and SOX4 knockdown during NEUROG2-driven fibroblast reprogramming

    PMID:28157484

    Open questions at the time
    • Whether NEUROG2 pioneer activity requires specific chromatin remodelers not determined in this study
    • Quantitative contribution of NEUROG2 versus small molecules to chromatin opening not deconvolved
  10. 2018 Medium

    Revealing a hierarchical phospho-regulatory switch — where bHLH-domain phosphorylation dominates over N/C-terminal multisite phosphorylation — established that Neurog2 integrates multiple kinase inputs with a defined logic gate controlling activity.

    Evidence Combined phospho-mutant Ngn2 constructs tested functionally in Xenopus embryos

    PMID:30430141

    Open questions at the time
    • Identity of the kinase targeting the bHLH domain not established
    • Whether this hierarchy operates in mammalian neurogenesis not tested
    • Structural basis for dominant inhibition not resolved
  11. 2019 High

    Genome-wide binding comparisons showed that Neurog2 and Ascl1 bind largely distinct genomic sites determined by intrinsic E-box sequence preferences of their DNA-binding domains, resolving the basis for their divergent neuronal fate outputs and establishing that pioneer activity reflects sequence selectivity rather than chromatin permissiveness.

    Evidence ChIP-seq and ATAC-seq for Ascl1 and Neurog2 during ESC-to-neuron reprogramming

    PMID:31086315

    Open questions at the time
    • Whether cofactor interactions contribute to genomic site selection beyond E-box preference not resolved
    • How binding-site divergence maps onto specific neuronal subtype transcriptomes not fully defined
  12. 2019 High

    Demonstrating that Neurog2 and Ascl1 cooperatively regulate a derepression circuit controlling neocortical laminar fate (Tbr1/Ctip2 versus Satb2) placed Neurog2 within a combinatorial logic governing temporal identity transitions in cortical progenitors.

    Evidence Neurog2;Ascl1 double knockout, stable gain-of-function transgenics, and acute misexpression in cortical progenitors

    PMID:28584103

    Open questions at the time
    • Direct versus indirect targets within the derepression circuit not fully mapped by ChIP
    • Whether other bHLH factors substitute in later cortical waves unknown
  13. 2020 High

    Identification of Fbxo9 as a Sox10-induced SCF-type E3 ligase that ubiquitylates and destabilizes Neurog2 protein resolved how glial versus neuronal fate decisions in neural crest are executed post-translationally, complementing earlier observations of non-canonical ubiquitylation.

    Evidence Co-IP, ubiquitylation assays, gain/loss-of-function, and Sox10–Fbxo9–Neurog2 epistasis in avian neural crest

    PMID:32029586

    Open questions at the time
    • Whether Fbxo9 targets cysteine or lysine residues on Neurog2 not distinguished
    • Relevance of Fbxo9 pathway in CNS neurogenesis not tested
  14. 2022 High

    Multi-modal epigenomic profiling in developing neocortex confirmed that Neurog2 directly mediates enhancer activation, DNA demethylation, and chromatin looping in vivo, extending pioneer factor function from reprogramming contexts to physiological cortical development.

    Evidence Single-cell ATAC-seq, scRNA-seq, H3K27ac ChIP, DNA methylation profiling, and Hi-C in mouse neocortex

    PMID:35132236

    Open questions at the time
    • Causal necessity of Neurog2 for each epigenomic change (demethylation, looping) not individually tested by acute conditional deletion
    • Chromatin remodeler partners mediating these changes not identified in vivo
  15. 2023 High

    CRISPR screening and scRNA-seq revealed that Neurog2, unlike Ascl1, drives neuronal reprogramming through a neural stem cell-like intermediate with incomplete pluripotency shutdown, explaining their mechanistically distinct reprogramming paths and differential dependency on Tcf7l1 for cell cycle exit.

    Evidence Genome-wide CRISPR-Cas9 knockout screen, scRNA-seq, and Cdkn1c epistasis during ESC-to-neuron conversion

    PMID:37660160

    Open questions at the time
    • Whether the neural stem cell intermediate arises during normal development or is a reprogramming artifact not resolved
    • Neurog2-specific genetic dependencies beyond Tcf7l1 not deeply characterized
  16. 2023 High

    Establishing that Neurog2 represses Isl1 through E-box elements in the Isl1 5'UTR, with natural SNP variation modulating this repression, revealed a quantitative genetic mechanism for Neurog2-dependent control of retinal horizontal cell number.

    Evidence QTL epistasis in recombinant inbred mice, conditional double knockout, and E-box reporter assays with SNP-level resolution

    PMID:36537573

    Open questions at the time
    • Whether Neurog2–Isl1 repression operates in other retinal or CNS cell types not tested
    • Mechanism of repression (direct binding or cofactor recruitment) at endogenous Isl1 locus not shown by ChIP

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the identity of chromatin remodeling complexes that mediate Neurog2's pioneer activity in vivo, the structural basis for Neurog2's E-box selectivity and phospho-regulatory hierarchy, and how cysteine versus lysine ubiquitylation differentially control Neurog2 turnover dynamics during fate decisions.
  • No in vivo structure of Neurog2/E47 on DNA
  • Chromatin remodeler identity (SWI/SNF, NuRD) confirmed only in preprint, not peer-reviewed
  • Relative contributions of Fbxo9 versus non-canonical cysteine ubiquitylation to Neurog2 degradation kinetics not compared

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
Pathway
R-HSA-74160 Gene expression (Transcription) 6 R-HSA-1266738 Developmental Biology 5 R-HSA-4839726 Chromatin organization 3 R-HSA-162582 Signal Transduction 2 R-HSA-1640170 Cell Cycle 1
Partners
ASCL1E47FBXO9MTGR1PAX3SOX4

Evidence

Reading pass · 27 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 Neurog2 functions as a permissive factor in neuronal subtype specification, requiring combinatorial action with other determinants rather than acting as an instructive determinant alone. Genetic swap experiments showed that Mash1 placed in Ngn2-expressing progenitors can respecify neuronal identity, but Ngn2 in Mash1 progenitors does not, demonstrating divergent instructive vs. permissive roles. Knock-in replacement mutations in mice (Mash1 and Ngn2 coding sequences swapped); loss-of-function and gain-of-function genetic epistasis Genes & development High 11825874
2005 Ngn2 modulates the composition of dorsal spinal cord interneuron populations (dI3, dI5) but is not required for any specific neuronal cell type; Mash1 is epistatic to Ngn2 in this context, and cross-repression of expression between the two factors is not detected. Loss-of-function mouse genetics (Mash1 and Ngn2 single/double mutants); genetic epistasis analysis Development (Cambridge, England) High 15901662
2008 Pax3 directly binds to cis-regulatory elements within the Ngn2 promoter and regulates Ngn2 transcription. This was demonstrated by promoter-luciferase assays, EMSA, and chromatin immunoprecipitation from neural tube tissue. Promoter-luciferase reporter assays, electrophoretic mobility shift assay (EMSA), chromatin immunoprecipitation (ChIP) Developmental biology High 18308300
2008 Ngn2 expression in neocortical daughter cells is initiated asymmetrically, with bias toward the apical daughter cell, and Tbr2 is a direct transcriptional target of Ngn2. Notch signaling (via gamma-secretase) in nascent daughter cells suppresses the Ngn2-Tbr2 cascade. DiI-labeled daughter cell tracking in slice cultures; gamma-secretase inhibition; immunostaining for Ngn2 and Tbr2; transgenic reporter analysis Molecular and cellular neurosciences Medium 19059340
2009 Neurog2 is a direct transcriptional target of the PTF1-J complex (Ptf1a + Rbpj). A 3' enhancer of Neurog2 requires a PTF1-J binding site for dorsal neural tube activity; Ptf1a gain- and loss-of-function modulate Neurog2 enhancer activity; ChIP from neural tube tissue confirms Ptf1a occupancy at the Neurog2 enhancer. Enhancer-reporter transgenic assays in mouse and chick; in vivo gain/loss-of-function; chromatin immunoprecipitation from neural tube tissue Development (Cambridge, England) High 19641016
2009 MTGR1, a transcriptional repressor induced by NEUROG2, physically interacts with NEUROG2, represses its transcriptional activity, and prevents DNA binding of the NEUROG2/E47 complex, forming a negative feedback loop that terminates NEUROG2 activity during neurogenesis. Co-immunoprecipitation (physical interaction); transcription assays; DNA binding assays; in vivo functional analysis in developing spinal cord Molecular and cellular neurosciences High 19646530
2009 Ascl1 and Neurog2 regulate expression of Delta-like 3 (Dll3) in the dorsal neural tube through distinct E-box elements in the Dll3 proximal promoter. Novel Ascl1/Ascl1 homodimer and Ascl1/Neurog2 heterodimer complexes bind specific E-box sites within this promoter in vitro. Transgenic reporter assays; E-box mutagenesis; in vitro DNA binding (EMSA-type); loss-of-function mouse genetics Developmental biology High 19389376
2010 Neurog2 is required for the leading edge of retinal neurogenesis; in its absence, the spread of neurogenesis and Atoh7 expression stalls, and this defect is eventually rescued by onset of Ascl1 expression, establishing a redundant/compensatory relationship between the two proneural genes in retinal neurogenesis. Loss-of-function mouse genetics (Neurog2 null); immunostaining; in vivo epistasis with Ascl1 Developmental biology High 20144606
2010 Ngn2 is ubiquitylated on non-canonical sites (cysteines) in addition to canonical lysines in both Xenopus embryo extracts and mammalian P19 cells; mutation of cysteines alone stabilizes Ngn2 protein, indicating non-canonical ubiquitylation on cysteine residues contributes to fast turnover of Ngn2. In vitro ubiquitylation assays in Xenopus extracts and P19 cells; site-directed mutagenesis of cysteines; protein stability assays Biochemical and biophysical research communications Medium 20807509
2010 Pax3 acetylation on C-terminal lysine residues K437 and K475 regulates Ngn2 promoter activity: removal of these lysines decreased Ngn2 promoter activity. SIRT1 deacetylase associates with the Ngn2 promoter in vivo (shown by ChIP), and SIRT1 overexpression decreases Pax3 acetylation and reduces Ngn2 expression; SIRT1 siRNA knockdown increases Ngn2 activity. Promoter-luciferase assays; site-directed mutagenesis of Pax3 lysines; ChIP for SIRT1 at Ngn2 promoter; siRNA knockdown and overexpression of SIRT1 Molecular biology of the cell High 21169561
2010 Folic acid reverses increased H3K27 methylation at the Neurog2 promoter in Splotch embryos partly via regulation of the demethylase KDM6B; KDM6B association with the Neurog2 promoter is inversely correlated with H3K27me2 levels, linking epigenetic H3K27 methylation to Neurog2 transcriptional regulation during neural tube development. Chromatin immunoprecipitation (ChIP) for H3K27me2 and KDM6B at Neurog2 promoter in embryonic neural tube tissue; in vivo folate rescue experiments The Journal of biological chemistry Medium 20833714
2010 MTG family members MTGR1 and MTG16 (but less efficiently MTG8) interact with and inhibit both NEUROG2 and ASCL1. Deletion mapping of MTGR1 shows that multiple conserved domains are required for binding and repression of NEUROG2, and that all conserved domains are needed for full repressor activity. Transcription reporter assays; co-immunoprecipitation; deletion mapping; ectopic expression in chick spinal cord Neuroscience letters Medium 20214951
2012 CDK-dependent multisite phosphorylation of Ngn2 differentially regulates its activity on distinct target promoters: the NeuroD promoter is substantially more sensitive to Ngn2 phosphorylation status than the Delta promoter. Phosphorylation of Ngn2 reduces its promoter binding affinity, and de-phosphorylation specifically enhances neuronal differentiation (via NeuroD) without proportionally increasing Delta-Notch signaling. Phosphorylation status also regulates Ngn2's sensitivity to Notch signaling. Phospho-mutant Ngn2 constructs; promoter reporter assays in Xenopus embryos and mouse P19 cells; functional phenotypic readouts Development (Cambridge, England) High 22491944
2012 NEUROG2 drives cell cycle exit of neuronal precursors by transcriptionally repressing a subset of cyclins (CCND1, CCNE1/2, CCNA2 but not CCND2) acting at G1 and S phases. NEUROG2 represses CCND1 and CCNE2 indirectly and possibly directly represses CCNE2; this cyclin repression prevents S phase entry and promotes cell cycle exit. Cell cycle exit can be uncoupled from neuronal differentiation. Large-scale chicken embryo gain-of-function strategy; NEUROG2VP16 (constitutive activator) and NEUROG2EnR (constitutive repressor) constructs; gene expression profiling; phenotypic analysis of S phase entry Molecular and cellular biology High 22547683
2016 NEUROG2 functions as a pioneer transcription factor during fibroblast-to-neuron reprogramming. NEUROG2 establishes initial open chromatin, and small molecules (forskolin and dorsomorphin) enhance chromatin accessibility and H3K27 acetylation synergistically with NEUROG2. CREB1 promotes neuron survival and co-activates SOX4 with NEUROG2; SOX4 then co-activates NEUROD1 and NEUROD4, targets SWI/SNF subunits, and is required for maintenance of open chromatin during reprogramming. ATAC-seq, ChIP-seq (H3K27ac), RNA-seq, SOX4 knockdown, reprogramming assays with NEUROG2 overexpression in fibroblasts Stem cell reports High 28157484
2018 hsa-miR-34a downregulates NEUROG2 by binding to its 5'-untranslated region, as demonstrated by luciferase reporter assays. NEUROG2 in turn activates its target RND2, placing NEUROG2 in a miR-34a → NEUROG2 → RND2 regulatory axis relevant to neuronal differentiation and migration. Luciferase reporter assays; in vitro validation; in situ hybridization; quantitative PCR Annals of neurology Medium 29461643
2018 Phosphorylation in the bHLH domain of Ngn2 (mimicking atonal-type single-site phosphorylation) dominates over the activating effects of preventing multisite N- and C-terminal phosphorylation. Combining a phospho-resistant bHLH domain mutation with phospho-mimetic N/C-terminal sites shows the bHLH-domain phosphorylation acts as a dominant inhibitory switch, establishing a hierarchy between two modes of proneural protein phospho-regulation. Combined activating and inhibitory phospho-mutant Ngn2 constructs; in vivo functional assay in Xenopus embryos Wellcome open research Medium 30430141
2019 Neurog2 and Ascl1 induce different neuronal fates by binding largely distinct sets of genomic sites. Their divergent binding patterns are determined by enrichment of specific E-box sequences reflecting differences in their DNA-binding domain preferences, not by prior chromatin state. Divergent binding results in distinct chromatin accessibility and enhancer activity profiles that differentially shape downstream transcription factor binding during differentiation. Direct neuronal programming of embryonic stem cells; ChIP-seq and ATAC-seq for Ascl1 and Neurog2; comparative genome-wide binding analysis Nature neuroscience High 31086315
2019 ETV5 represses NEUROG2 transcription in neural progenitor cells via the NEUROG2 promoter in an ETS-domain-dependent manner, recruiting the co-repressor CoREST. ChIP assays show ETV5 occupancy at the NEUROG2 promoter within silent chromatin, and NEUROG2 repression by ETV5 blocks glutamatergic neuron generation while promoting GABAergic output. Luciferase reporter assays; ChIP assays; siRNA knockdown and overexpression; co-repressor (CoREST) interaction Stem cell reviews and reports Medium 31273540
2019 Neurog2 and Ascl1 together regulate a derepression circuit controlling laminar fate in the neocortex: Neurog2 and Ascl1 co-operate in progenitors to extend deep-layer neurogenesis (Tbr1+/Ctip2+) and suppress premature Satb2+ upper-layer differentiation. Neurog2 misexpression in early progenitors promotes Tbr1 expression, while both Neurog2 and Ascl1 can induce Ctip2. Loss of both proneural genes disrupts the derepression circuit regulating Tbr1, Fezf2, Satb2, and Ctip2. Loss-of-function (Neurog2;Ascl1 double mutants); stable gain-of-function transgenics; acute misexpression in cortical progenitors; immunostaining Proceedings of the National Academy of Sciences of the United States of America High 28584103
2020 Sox10 promotes glial fate over neuronal fate in dorsal root ganglia neural crest progenitors by upregulating Fbxo9, an SCF-type ubiquitin E3 ligase that interacts with Neurog2 via its F-box motif and promotes Neurog2 ubiquitination and protein destabilization. Fbxo9 overexpression decreases Neurog2 protein and promotes glial fate; Fbxo9 knockdown does the opposite. Epistasis places Fbxo9 downstream of Sox10 in the Neurog2 destabilization pathway. Gain- and loss-of-function in avian neural crest; Co-IP (Fbxo9-Neurog2 interaction); ubiquitination assay; transcriptional profiling; epistasis analysis Proceedings of the National Academy of Sciences of the United States of America High 32029586
2020 WNT/β-catenin activation in pMN lineage cells abolishes Olig2 expression coupled with increased Ngn2 expression. Ngn2 directly represses Olig2 promoter activity (shown by luciferase reporter assay); overexpression of Ngn2-EnR repressor blocks Olig2 expression in ovo, placing Ngn2 as a direct transcriptional repressor of Olig2 downstream of WNT signaling. Luciferase reporter assay; Ngn2-EnR construct in ovo; WNT pathway activation in neural progenitors Molecular brain Medium 33187539
2022 Neurog2 directly mediates enhancer activity, DNA demethylation, increased chromatin accessibility, and chromatin looping in vivo in the developing mouse neocortex, as functionally demonstrated by multimodal profiling. Neurog2 acts as a key epigenome remodeler during cortical neuronal differentiation. Single-cell ATAC-seq, single-cell RNA-seq, bulk enhancer activity (H3K27ac), DNA methylation profiling, Hi-C/3D genome architecture, and in vivo functional validation in neocortex Nature neuroscience High 35132236
2023 Ascl1 and Ngn2 convert mouse embryonic stem cells to neurons via mechanistically distinct paths: Ascl1 rapidly dismantles the pluripotency network and directly installs neuronal fate, while Ngn2 generates a neural stem cell-like intermediate supported by incomplete shutdown of pluripotency. CRISPR-Cas9 knockout screening shows Ascl1, but not Ngn2, relies critically on Tcf7l1 for cell cycle exit; Tcf7l1 loss prevents Ascl1-driven cell cycle exit which can be rescued by Cdkn1c overexpression. CRISPR-Cas9 genome-wide knockout screening; scRNA-seq; direct reprogramming assays; epistasis with Cdkn1c overexpression Nature communications High 37660160
2023 Neurog2 regulates retinal horizontal cell number by repressing the LIM homeodomain transcription factor Isl1. Epistasis between chromosome 3 (Neurog2) and chromosome 13 (Isl1) loci was established in recombinant inbred mice; conditional double KO confirmed countervailing actions. In vitro reporter assays validated that two SNPs in the 5'UTR of Isl1 (one creating a novel E-box) mediate Neurog2's repressive action on Isl1. QTL mapping in recombinant inbred strains; conditional single and double knockout mice; in vitro E-box reporter assays; SNP functional validation Development (Cambridge, England) High 36537573
2024 Neurog2 binding to chromatin is determined by cell-type-specific chromatin accessibility and motif syntax (E-box sequence context), not prior chromatin state alone. Neurog2 binding primarily leads to chromatin opening, DNA demethylation, and increased chromatin interactions, with strong indirect cell-type-specific effects. Neurog2 interacts with the SWI/SNF and NuRD complexes, identified as cell-type-specific interactors. ChIP-seq, ATAC-seq, DNA methylation profiling, Hi-C, and co-immunoprecipitation/mass spectrometry in mouse ESCs and neural progenitor cells bioRxivpreprint Medium
2014 Notch1 and Rbpj normally repress Neurog2 expression in the distal retina; the combined activities of Notch1, Notch3, and Rbpj (but not Hes1, Hes3, or Hes5) regulate Neurog2 patterning. This distinguishes Neurog2 from Atoh7, whose suppression is mediated specifically by Hes1, revealing non-overlapping downstream effectors of Notch signaling for these two bHLH factors. Broad spectrum Notch pathway mutants in mouse (Notch1, Notch3, Rbpj, Hes1/3/5 single and compound mutants); immunostaining; genetic epistasis Development (Cambridge, England) High 25100656

Source papers

Stage 0 corpus · 92 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Divergent functions of the proneural genes Mash1 and Ngn2 in the specification of neuronal subtype identity. Genes & development 301 11825874
2018 Combining NGN2 Programming with Developmental Patterning Generates Human Excitatory Neurons with NMDAR-Mediated Synaptic Transmission. Cell reports 213 29791859
2015 Rapid Ngn2-induction of excitatory neurons from hiPSC-derived neural progenitor cells. Methods (San Diego, Calif.) 128 26626326
2016 Small Molecules Modulate Chromatin Accessibility to Promote NEUROG2-Mediated Fibroblast-to-Neuron Reprogramming. Stem cell reports 107 28157484
2005 Sequential roles for Mash1 and Ngn2 in the generation of dorsal spinal cord interneurons. Development (Cambridge, England) 103 15901662
2019 Proneural factors Ascl1 and Neurog2 contribute to neuronal subtype identities by establishing distinct chromatin landscapes. Nature neuroscience 99 31086315
2021 NGN2 induces diverse neuron types from human pluripotency. Stem cell reports 96 34358451
2009 Ascl1 and Neurog2 form novel complexes and regulate Delta-like3 (Dll3) expression in the neural tube. Developmental biology 89 19389376
2010 Neurog2 controls the leading edge of neurogenesis in the mammalian retina. Developmental biology 86 20144606
2008 Periventricular notch activation and asymmetric Ngn2 and Tbr2 expression in pair-generated neocortical daughter cells. Molecular and cellular neurosciences 83 19059340
2010 Folic acid remodels chromatin on Hes1 and Neurog2 promoters during caudal neural tube development. The Journal of biological chemistry 75 20833714
2012 Post-translational modification of Ngn2 differentially affects transcription of distinct targets to regulate the balance between progenitor maintenance and differentiation. Development (Cambridge, England) 73 22491944
2009 Involvement of Ngn2, Tbr and NeuroD proteins during postnatal olfactory bulb neurogenesis. The European journal of neuroscience 69 19200230
2011 Sequential generation of olfactory bulb glutamatergic neurons by Neurog2-expressing precursor cells. Neural development 64 21466690
2012 NEUROG2 drives cell cycle exit of neuronal precursors by specifically repressing a subset of cyclins acting at the G1 and S phases of the cell cycle. Molecular and cellular biology 61 22547683
2007 Proliferating neuronal progenitors in the postnatal hippocampus transiently express the proneural gene Ngn2. The European journal of neuroscience 61 17466019
2006 Ngn2 and Nurr1 act in synergy to induce midbrain dopaminergic neurons from expanded neural stem and progenitor cells. Experimental cell research 59 17291494
2008 Key basic helix-loop-helix transcription factor genes Hes1 and Ngn2 are regulated by Pax3 during mouse embryonic development. Developmental biology 58 18308300
2008 Effects on differentiation of embryonic ventral midbrain progenitors by Lmx1a, Msx1, Ngn2, and Pitx3. The Journal of neuroscience : the official journal of the Society for Neuroscience 58 18385323
2022 Multimodal profiling of the transcriptional regulatory landscape of the developing mouse cortex identifies Neurog2 as a key epigenome remodeler. Nature neuroscience 53 35132236
2014 Neurog1 and Neurog2 control two waves of neuronal differentiation in the piriform cortex. The Journal of neuroscience : the official journal of the Society for Neuroscience 51 24403153
2009 Neurog2 is a direct downstream target of the Ptf1a-Rbpj transcription complex in dorsal spinal cord. Development (Cambridge, England) 48 19641016
2010 Role of Pax3 acetylation in the regulation of Hes1 and Neurog2. Molecular biology of the cell 39 21169561
2017 Neurog2 and Ascl1 together regulate a postmitotic derepression circuit to govern laminar fate specification in the murine neocortex. Proceedings of the National Academy of Sciences of the United States of America 38 28584103
2023 Efficient generation of lower induced motor neurons by coupling Ngn2 expression with developmental cues. Cell reports 37 36596304
2012 Neurog1 and Neurog2 coordinately regulate development of the olfactory system. Neural development 37 22906231
2014 Notch signaling differentially regulates Atoh7 and Neurog2 in the distal mouse retina. Development (Cambridge, England) 36 25100656
2021 Neurog2 directly converts astrocytes into functional neurons in midbrain and spinal cord. Cell death & disease 35 33649354
2019 Overexpression of NEUROG2 and NEUROG1 in human embryonic stem cells produces a network of excitatory and inhibitory neurons. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 34 30698461
2004 Differential expression of Pax6 and Ngn2 between pair-generated cortical neurons. Journal of neuroscience research 29 15523634
2023 Ascl1 and Ngn2 convert mouse embryonic stem cells to neurons via functionally distinct paths. Nature communications 27 37660160
2010 Non-canonical ubiquitylation of the proneural protein Ngn2 occurs in both Xenopus embryos and mammalian cells. Biochemical and biophysical research communications 27 20807509
2019 ETV5 is Essential for Neuronal Differentiation of Human Neural Progenitor Cells by Repressing NEUROG2 Expression. Stem cell reviews and reports 26 31273540
2024 Fully defined NGN2 neuron protocol reveals diverse signatures of neuronal maturation. Cell reports methods 24 39255791
2022 Combining NGN2 programming and dopaminergic patterning for a rapid and efficient generation of hiPSC-derived midbrain neurons. Scientific reports 24 36229560
2021 Generation of two gene edited iPSC-lines carrying a DOX-inducible NGN2 expression cassette with and without GFP in the AAVS1 locus. Stem cell research 24 33610017
2018 Dysregulation of NEUROG2 plays a key role in focal cortical dysplasia. Annals of neurology 24 29461643
2021 Initiation of Otx2 expression in the developing mouse retina requires a unique enhancer and either Ascl1 or Neurog2 activity. Development (Cambridge, England) 23 34143204
2020 Neurog2 Acts as a Classical Proneural Gene in the Ventromedial Hypothalamus and Is Required for the Early Phase of Neurogenesis. The Journal of neuroscience : the official journal of the Society for Neuroscience 22 32273485
2018 Instructing neuronal identity during CNS development and astroglial-lineage reprogramming: Roles of NEUROG2 and ASCL1. Brain research 21 29510143
2017 DISC1 Regulates the Proliferation and Migration of Mouse Neural Stem/Progenitor Cells through Pax5, Sox2, Dll1 and Neurog2. Frontiers in cellular neuroscience 21 28900388
2013 Sustained vs. oscillating expressions of Ngn2, Dll1 and Hes1: a model of neural differentiation of embryonic telencephalon. Journal of theoretical biology 21 23499991
2012 Methylation status of NEUROG2 and NID2 improves the diagnosis of stage I NSCLC. Oncology letters 21 22741015
2023 Robust induction of functional astrocytes using NGN2 expression in human pluripotent stem cells. iScience 20 37534135
2015 Human Induced Pluripotent Stem Cell NEUROG2 Dual Knockin Reporter Lines Generated by the CRISPR/Cas9 System. Stem cells and development 20 26414932
2017 Neuroprotective effect of olfactory ensheathing cells co-transfected with Nurr1 and Ngn2 in both in vitro and in vivo models of Parkinson's disease. Life sciences 19 29291419
2004 E1-Ngn2/Cre is a new line for regional activation of Cre recombinase in the developing CNS. Genesis (New York, N.Y. : 2000) 18 15593326
2002 Expression of Ngn1, Ngn2, Cash1, Gsh2 and Sfrp1 in the developing chick telencephalon. Mechanisms of development 18 11744393
2021 Development of a fully human assay combining NGN2-inducible neurons co-cultured with iPSC-derived astrocytes amenable for electrophysiological studies. Stem cell research 17 34229210
2020 Fbxo9 functions downstream of Sox10 to determine neuron-glial fate choice in the dorsal root ganglia through Neurog2 destabilization. Proceedings of the National Academy of Sciences of the United States of America 16 32029586
2021 NGN2 mmRNA-Based Transcriptional Programming in Microfluidic Guides hiPSCs Toward Neural Fate With Multiple Identities. Frontiers in cellular neuroscience 15 33679325
2018 TAT-Ngn2 Enhances Cognitive Function Recovery and Regulates Caspase-Dependent and Mitochondrial Apoptotic Pathways After Experimental Stroke. Frontiers in cellular neuroscience 15 30618628
2013 Naturally occurring Ngn2 promoter activators from Butea superba. Molecular bioSystems 15 23903453
2019 Neurog2 Deficiency Uncovers a Critical Period of Cell Fate Plasticity and Vulnerability among Neural-Crest-Derived Somatosensory Progenitors. Cell reports 14 31801063
2007 Neurospheres derived from human embryoid bodies treated with retinoic Acid show an increase in nestin and ngn2 expression that correlates with the proportion of tyrosine hydroxylase-positive cells. Stem cells and development 14 17784840
2020 WNT signaling suppresses oligodendrogenesis via Ngn2-dependent direct inhibition of Olig2 expression. Molecular brain 13 33187539
2018 Direct Reprogramming of Adult Human Somatic Stem Cells Into Functional Neurons Using Sox2, Ascl1, and Neurog2. Frontiers in cellular neuroscience 13 29937717
2009 Feedback regulation of NEUROG2 activity by MTGR1 is required for progression of neurogenesis. Molecular and cellular neurosciences 13 19646530
2023 Activity-Dependent Transcriptional Program in NGN2+ Neurons Enriched for Genetic Risk for Brain-Related Disorders. Biological psychiatry 12 37454787
2014 Transcriptional regulatory events initiated by Ascl1 and Neurog2 during neuronal differentiation of P19 embryonic carcinoma cells. Journal of molecular neuroscience : MN 12 25189318
2015 Phenolic compounds from the bark of Oroxylum indicum activate the Ngn2 promoter. Journal of natural medicines 11 26014045
2022 Derivation of nociceptive sensory neurons from hiPSCs with early patterning and temporally controlled NEUROG2 overexpression. Cell reports methods 10 36452863
2011 Differential contribution of Neurog1 and Neurog2 on the formation of cranial ganglia along the anterior-posterior axis. Developmental dynamics : an official publication of the American Association of Anatomists 10 22102600
2024 Insights for disease modeling from single-cell transcriptomics of iPSC-derived Ngn2-induced neurons and astrocytes across differentiation time and co-culture. BMC biology 9 38566045
2015 Inubosins A, B, and C are acridine alkaloids isolated from a culture of Streptomyces sp. IFM 11440 with Ngn2 promoter activity. Journal of natural products 9 25621736
2022 Cend1 and Neurog2 efficiently reprogram human cortical astrocytes to neural precursor cells and induced-neurons. The International journal of developmental biology 8 34549796
2010 Interaction of MTG family proteins with NEUROG2 and ASCL1 in the developing nervous system. Neuroscience letters 8 20214951
2022 TAT-LBD-Ngn2-improved cognitive functions after global cerebral ischemia by enhancing neurogenesis. Brain and behavior 7 36495119
2023 Disruption of DDX53 coding sequence has limited impact on iPSC-derived human NGN2 neurons. BMC medical genomics 6 36635662
2023 Engineered neurogenesis in naïve adult rat cortex by Ngn2-mediated neuronal reprogramming of resident oligodendrocyte progenitor cells. Frontiers in neuroscience 6 37662111
2021 Transcriptomic data of Clozapine-treated Ngn2-induced Human Excitatory Neurons. Data in brief 5 33681435
2019 Generation of a knock-in MAP2-tdTomato reporter human embryonic stem cell line with inducible expression of NEUROG2/1 (NYGCe001-A). Stem cell research 5 31707212
2025 Protocol for generating NGN2 iPSC lines and large-scale human neuron production. STAR protocols 4 40022736
2024 Generation of a gene-edited H9 embryonic stem cell line carrying a DOX-inducible NGN2 expression cassette in the CLYBL locus. Stem cell research 4 38244534
2009 Genetic analysis of the NEUROG2 gene in patients with Parkinson's disease. Neuroscience letters 4 19879328
2024 Generation of three isogenic gene-edited Huntington's disease human embryonic stem cell lines with DOX-inducible NGN2 expression cassette in the AAVS1 safe locus. Stem cell research 3 38569398
2023 Neurog2 regulates Isl1 to modulate horizontal cell number. Development (Cambridge, England) 3 36537573
2020 Transcriptional activity of FIGLA, NEUROG2, and EGR1 transcription factors associated with polymorphisms in the proximal regulatory region of GPR54 gene in cattle. Animal reproduction science 3 32507252
2018 Interaction between opposing modes of phospho-regulation of the proneural proteins Ascl1 and Ngn2. Wellcome open research 3 30430141
2025 BMP, MEK, and WNT inhibition with NGN2 expression for rapid generation of hiPSC-derived neurons amenable to regional patterning. Stem cell reports 2 40541177
2023 NGN2-based neuronal programming of hiPSCs in an automated microfluidic platform. Biochemical and biophysical research communications 2 37178505
2025 Ngn2-Induced Differentiation of the NG108-15 Cell Line Enhances Motor Neuronal Differentiation and Neuromuscular Junction Formation. Biomolecules 1 40427530
2025 Extended NGN2 Expression in iPSCs Dramatically Enhances Purity of Neuronal Cultures. bioRxiv : the preprint server for biology 1 40667215
2024 Decoding single-cell molecular mechanisms in astrocyte-to-iN reprogramming via Ngn2- and Pax6-mediated direct lineage switching. European journal of medical research 1 39068473
2024 SOXC Enhances NGN2-Mediated Reprogramming of Glioblastoma Cells Into Neuron-Like Cells by Modulating RhoA and RAC1/CDC42 Pathway Activity. CNS neuroscience & therapeutics 1 39390804
2026 Early Reprogramming Intermediates Enable Direct Neuronal Conversion Via NGN2. Journal of molecular neuroscience : MN 0 41632409
2026 Generation of two tetracycline-inducible NGN2 iN iPSC lines carrying a heterozygous floating-Harbor syndrome SRCAP truncating mutation. Stem cell research 0 41655494
2025 A novel role for Neurog2 in MYCN driven neuroendocrine plasticity of prostate cancer. Oncogene 0 40301542
2025 Ngn2 and Isl1-mediated astrocyte-to-neuron conversion in vivo promotes functional recovery after spinal cord injury. Cell reports. Medicine 0 41265444
2025 Correction: Meli et al. Ngn2-Induced Differentiation of the NG108-15 Cell Line Enhances Motor Neuronal Differentiation and Neuromuscular Junction Formation. Biomolecules 2025, 15, 637. Biomolecules 0 41463407
2024 A Snapshot of Early Transcriptional Changes Accompanying the Pro-Neural Phenotype Switch by NGN2, ASCL1, SOX2, and MSI1 in Human Fibroblasts: An RNA-Seq Study. International journal of molecular sciences 0 39596450
2016 Distribution of pancreatic B cell imaging agent (99m)Tc-DTPA-NGN2 in the body and animal experimental research on pancreatic B cell functional imaging. American journal of translational research 0 27186309