Affinage

ASCL1

Achaete-scute homolog 1 · UniProt P50553

Length
236 aa
Mass
25.5 kDa
Annotated
2026-04-28
100 papers in source corpus 33 papers cited in narrative 33 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ASCL1 is a basic helix-loop-helix (bHLH) proneural transcription factor that functions as a pioneer factor, binding specific E-box sequences to open closed chromatin and activate neuronal and neuroendocrine gene expression programs across diverse cellular contexts (PMID:28712938, PMID:31086315, PMID:36931659). ASCL1 cooperates with BAF/SWI-SNF chromatin remodeling complexes at permissive chromatin sites and with lineage-specifying partner transcription factors—including NKX2-1/PROX1 in small cell lung cancer, PHOX2B/GATA3 in neuroblastoma, and MEF2C in cardiac reprogramming—that redirect its genomic binding from neuronal to alternative lineage targets (PMID:36931659, PMID:34466783, PMID:36263020, PMID:36206732). Its activity is tuned by oscillatory expression dynamics downstream of Notch/Hes1 signaling, by serine-proline phosphorylation that favors proliferation over differentiation, and by subcellular-compartment-specific ubiquitylation wherein cytoplasmic Huwe1-mediated ubiquitylation drives degradation while chromatin-associated short ubiquitin chains preserve ASCL1 function (PMID:30862661, PMID:35149717, PMID:29545540). ASCL1 is required for neuroendocrine lineage identity and tumor initiation in small cell lung cancer and neuroendocrine prostate cancer, where its loss abolishes neuroendocrine differentiation and shifts cells toward alternative lineage states (PMID:27452466, PMID:39394434, PMID:34016693).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 2000 Medium

    Establishing that ASCL1 transcription is directly repressed by HES1 through N-box binding placed ASCL1 downstream of Notch signaling, answering how Notch activation suppresses neuronal differentiation at the promoter level.

    Evidence EMSA showing HES1 binding to ASCL1 promoter N-box, Notch1-ICD overexpression in neuroblastoma cells

    PMID:11054669

    Open questions at the time
    • No ChIP confirmation of HES1 occupancy at endogenous ASCL1 promoter in vivo
    • Kinetics of HES1-mediated repression not resolved
  2. 2011 Medium

    Identification of miR-375 as a direct ASCL1 transcriptional target that represses YAP1 revealed a non-coding RNA effector arm through which ASCL1 promotes neuroendocrine features in lung cancer.

    Evidence shRNA knockdown of ASCL1, miR-375 manipulation, luciferase reporter assays in NE lung cancer lines

    PMID:21856745

    Open questions at the time
    • Direct ASCL1 binding to miR-375 regulatory region not shown by ChIP at this stage
    • Contribution of miR-375 relative to other ASCL1 targets unclear
  3. 2013 High

    Conditional deletion studies demonstrated that ASCL1 is required not only for neuronal specification (inhibitory dorsal horn interneurons) but also for oligodendrocyte precursor cell specification and remyelination, broadening its known lineage roles beyond neurons.

    Evidence Conditional Ascl1 KO in cortical/OPC progenitors and spinal dorsal horn, lineage tracing, demyelination model

    PMID:23616538 PMID:23739972

    Open questions at the time
    • Direct transcriptional targets mediating OPC vs. neuronal specification not distinguished
    • Whether ASCL1 binding sites differ in OPC vs. neuronal progenitors was unknown
  4. 2013 High

    Demonstration that FOXO3 co-occupies ASCL1-bound enhancers and antagonizes ASCL1-dependent neurogenesis established a paradigm for how signaling pathways modulate ASCL1 pioneer activity through co-factor competition at shared genomic targets.

    Evidence ChIP-seq for FOXO3 and ASCL1 in neural progenitor cells, loss-of-function in NPCs/fibroblasts, in vivo neurogenesis

    PMID:23891001

    Open questions at the time
    • Molecular mechanism of FOXO3 antagonism (competition vs. active repression) not resolved
    • Whether FOXO3 blocks ASCL1 chromatin opening specifically was untested
  5. 2016 High

    Genome-wide ChIP-seq in SCLC revealed that ASCL1 and NEUROD1 define distinct transcriptional subgroups by binding largely non-overlapping genomic sites, establishing ASCL1 as a master regulator of a specific SCLC oncogenic program including MYCL1, RET, and DLL3.

    Evidence ChIP-seq and RNA-seq in human SCLC lines, shRNA knockdown, mouse SCLC GEMMs

    PMID:27452466

    Open questions at the time
    • How ASCL1 vs. NEUROD1 binding specificity is determined at the DNA/protein level was unknown
    • Whether ASCL1 acts as a pioneer factor in SCLC was not yet addressed
  6. 2017 High

    ATAC-seq and ChIP-seq in glioblastoma stem cells provided the first direct evidence that ASCL1 functions as a pioneer factor, opening previously closed chromatin to activate a neurogenic differentiation program and suppress tumorigenicity.

    Evidence ATAC-seq/ChIP-seq after lentiviral ASCL1 expression in patient-derived GBM stem cells, in vivo tumor assays

    PMID:28712938

    Open questions at the time
    • Whether pioneer activity requires cofactors or is intrinsic to ASCL1 was not dissected
    • Mechanism of chromatin opening (nucleosome displacement vs. remodeler recruitment) unresolved
  7. 2018 High

    Biochemical dissection of ASCL1 ubiquitylation revealed that subcellular location dictates its post-translational fate: cytoplasmic Huwe1-mediated ubiquitylation on bHLH-domain lysines drives degradation, while chromatin-bound ASCL1 carries short non-degradative ubiquitin chains on distinct residues.

    Evidence Subcellular fractionation, ubiquitin IP, lysine-to-arginine mutagenesis, Huwe1 knockdown

    PMID:29545540

    Open questions at the time
    • Function of non-degradative chromatin-associated ubiquitin chains unknown
    • E3 ligase responsible for chromatin-associated ubiquitylation not identified
  8. 2019 High

    Comparison of ASCL1 and Neurog2 binding in ES cell-derived neurons showed that divergent neuronal fates arise from intrinsic E-box sequence preferences of the bHLH DNA-binding domains rather than from prior chromatin states, resolving how two pioneer factors accessing closed chromatin produce distinct outcomes.

    Evidence ChIP-seq, ATAC-seq, E-box motif analysis during directed neuronal programming from ESCs

    PMID:31086315

    Open questions at the time
    • Structural basis for differential E-box recognition not determined
    • Whether cofactor interactions modulate E-box selectivity in vivo untested
  9. 2019 High

    Live imaging of Hes1/Ascl1 oscillatory dynamics in adult neural stem cells demonstrated that oscillatory (low-amplitude) Ascl1 expression maintains proliferative capacity while sustained high expression drives differentiation, establishing expression dynamics as a functional switch.

    Evidence Live-cell imaging, conditional Hes1 genetic manipulation, Ascl1 induction in adult mouse brain

    PMID:30862661

    Open questions at the time
    • How oscillatory vs. sustained ASCL1 protein levels differentially engage target genes mechanistically was unresolved
    • Post-translational regulation during oscillations not examined
  10. 2020 High

    STAT signaling in injured Müller glia was shown to redirect Ascl1 binding to developmentally inappropriate chromatin targets, establishing that the signaling environment can reprogram pioneer factor genomic occupancy and limit regenerative neurogenesis.

    Evidence Ascl1 ChIP-seq ± STAT inhibition in Müller glia, single-cell RNA-seq, ATAC-seq

    PMID:32075759

    Open questions at the time
    • Whether STAT factors physically interact with ASCL1 or act indirectly via chromatin remodeling unknown
    • Generalizability to other injury contexts not tested
  11. 2021 High

    Identification of ASCL1 cooperation with NKX2-1 and PROX1 as co-occupying transcription factors at super-enhancers in SCLC, combined with in vivo demonstration that ASCL1 loss derepresses a SOX9+ mesenchymal program while being required for NE identity, defined ASCL1 as both an activator of NE lineage and a repressor of alternative fates.

    Evidence ChIP-seq, Co-IP for ASCL1/NKX2-1/PROX1, conditional Ascl1 deletion in SCLC GEMMs, RNA-seq

    PMID:34016693 PMID:34466783

    Open questions at the time
    • Stoichiometry and assembly order of ASCL1/NKX2-1/PROX1 complex unknown
    • Whether ASCL1 actively recruits repressive machinery to SOX9 loci or acts indirectly unclear
  12. 2022 High

    ASCL1 was established as a driver of neuroendocrine lineage plasticity in prostate cancer through chromatin remodeling involving a PRC2/UHRF1/AMPK axis, and partner-dependent redirection of ASCL1 binding by MEF2C toward cardiac genes demonstrated that ASCL1 pioneer activity is fundamentally context-dependent.

    Evidence ATAC-seq/ChIP-seq in prostate cancer with ASCL1 knockdown and UHRF1/AMPK pathway perturbation; ChIP-seq during ASCL1+MEF2C cardiac reprogramming

    PMID:35477723 PMID:36206732

    Open questions at the time
    • Direct physical interaction between ASCL1 and PRC2 components not shown
    • How MEF2C mechanistically redirects ASCL1 DNA binding unclear
  13. 2023 High

    Endogenous ASCL1 knockout during human neural differentiation combined with SWI/SNF interaction studies revealed a dual mode: classical pioneer activity at closed chromatin and non-pioneer remodeling at permissive chromatin via BAF complex recruitment, resolving how ASCL1 engages chromatin through two mechanistically distinct pathways.

    Evidence ASCL1 KO hESC differentiation model, ATAC-seq, ChIP-seq, Co-IP for ASCL1-SWI/SNF

    PMID:36931659

    Open questions at the time
    • Which BAF complex subunits directly contact ASCL1 not mapped
    • Whether pioneer vs. non-pioneer mode distinction applies in cancer contexts unknown
  14. 2024 High

    Staged genetic deletion in prostate cancer models showed ASCL1 is required for initiating the neuroendocrine lineage transition from luminal cells but becomes partially dispensable in established tumors, revealing a temporal hierarchy in ASCL1 dependency for lineage plasticity.

    Evidence Mouse organoid transplantation with conditional Ascl1 deletion at different stages, spatial transcriptomics, multiplexed IF

    PMID:39264686 PMID:39394434

    Open questions at the time
    • Compensatory factors maintaining NE identity after ASCL1 loss in established tumors not identified
    • Whether ASCL1 re-expression drives re-emergence of NE phenotype untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis for ASCL1's differential E-box selectivity, the identity and function of the E3 ligase responsible for non-degradative chromatin-associated ubiquitylation, and how oscillatory vs. sustained ASCL1 expression differentially engages downstream targets at the molecular level.
  • No structural model of ASCL1 DNA-binding domain bound to preferred E-box variants
  • E3 ligase for chromatin-associated non-degradative ubiquitylation unknown
  • Molecular mechanism linking ASCL1 protein oscillation amplitude to target gene selection unresolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 9 GO:0003677 DNA binding 7 GO:0042393 histone binding 1
Localization
GO:0005634 nucleus 5 GO:0005694 chromosome 2 GO:0005829 cytosol 1
Pathway
R-HSA-74160 Gene expression (Transcription) 11 R-HSA-1266738 Developmental Biology 5 R-HSA-4839726 Chromatin organization 5 R-HSA-1640170 Cell Cycle 4 R-HSA-162582 Signal Transduction 3
Partners
FOXO3GSX2HES1HUWE1MEF2CNKX2-1PROX1TCF3
Complex memberships
BAF/SWI-SNF complex

Evidence

Reading pass · 33 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2016 ASCL1 binds distinct genomic loci and regulates mostly distinct genes compared to NEUROD1 in SCLC; ASCL1 targets oncogenic genes including MYCL1, RET, SOX2, NFIB, and multiple NOTCH pathway genes including DLL3, and is required in vivo for tumor formation in mouse models of SCLC. ChIP-seq, RNA-seq, mouse genetic models (SCLC), shRNA knockdown in human SCLC cell lines Cell reports High 27452466
2017 ASCL1 functions as a pioneer transcription factor in glioblastoma stem cells, opening closed chromatin regions to activate a neurogenic gene expression program, promoting terminal neuronal differentiation and suppressing tumorigenicity. ATAC-seq, ChIP-seq, lentiviral ASCL1 overexpression, Notch inhibition in patient-derived glioblastoma stem cells, in vivo tumor assays Cell stem cell High 28712938
2019 ASCL1 and Neurogenin2 (Neurog2) induce different neuronal fates by binding largely different genomic sites; divergent binding patterns are determined by enrichment of specific E-box sequences reflecting DNA-binding domain preferences, not prior chromatin state, leading to distinct chromatin accessibility and enhancer activity profiles. ChIP-seq, ATAC-seq, direct neuronal programming of embryonic stem cells, E-box motif analysis Nature neuroscience High 31086315
2013 FOXO3 shares common genomic targets with ASCL1 in adult neural progenitor cells, co-occupying enhancers of neurogenic pathway genes; FOXO3 inhibits ASCL1-dependent neurogenesis in neural progenitor cells and direct neuronal conversion in fibroblasts, and restrains neurogenesis in vivo. ChIP-seq (FOXO3 and ASCL1), ATAC-seq/chromatin landscape analysis, loss-of-function in NPCs and fibroblasts, in vivo neurogenesis assays Cell reports High 23891001
2011 ASCL1 (ASH1) transcriptionally activates miR-375 in neuroendocrine lung cancer cells; miR-375 is a downstream effector required for ASH1-mediated induction of neuroendocrine features, and miR-375 directly targets YAP1 to relieve YAP1-mediated growth inhibition. shRNA knockdown of ASH1, miR-375 overexpression/knockdown, luciferase reporter assays, western blotting in lung cancer cell lines Cancer research Medium 21856745
2012 hASH1 stimulates lung cancer cell migration through a Cdk5/p35 pathway; p35 is a direct transcriptional target of hASH1, and hASH1 expression increases p35/Cdk5 activity to enhance cellular migration. shRNA knockdown of hASH1, dominant-negative Cdk5 expression, Cdk5 inhibitor roscovitine, hASH1 overexpression in adenocarcinoma cells, ChIP for p35 promoter Molecular biology of the cell Medium 22696682
2010 ASCL1 regulates expression of the CHRNA5/A3/B4 nicotinic acetylcholine receptor gene cluster in small cell lung cancer; ASCL1 knockdown specifically reduced alpha3 and beta4 subunit expression without affecting other nAChR genes, indicating ASCL1-specific transcriptional regulation of this locus. shRNA knockdown of ASCL1 in SCLC and non-SCLC cell lines, qRT-PCR, in silico promoter analysis for ASCL1 binding sites Molecular cancer research Medium 20124469
2019 In adult mouse neural stem cells, oscillatory Hes1 expression drives cyclic Ascl1 expression to promote active proliferation; high sustained Hes1 expression continuously suppresses Ascl1 and promotes quiescence. Inactivation of Hes1 and related genes upregulates Ascl1 and increases neurogenesis, causing depletion of stem cells, while induction of Ascl1 oscillations activates stem cells. Genetic inactivation of Hes1 in mouse, live-cell imaging of Hes1/Ascl1 dynamics, conditional Hes1 overexpression, Ascl1 induction in adult mouse brain Genes & development High 30862661
2021 ASCL1 in SCLC cooperates with NKX2-1 and PROX1 to form complexes that co-regulate genes in NOTCH signaling, catecholamine biosynthesis, and cell-cycle processes; ASCL1 is a key dependency factor in SCLC preclinical models and directly regulates multiple essential genes. ChIP-seq, RNA-seq, super-enhancer mapping, ASCL1 depletion in SCLC models, co-immunoprecipitation iScience High 34466783
2013 Ascl1/Mash1 promotes oligodendrocyte precursor cell specification from subventricular zone progenitors and regulates the balance between OPC differentiation and proliferation in postnatal cortex; Ascl1 is required for proper remyelination, with remyelinating oligodendrocytes derived from Ascl1+ progenitors. Conditional genetic deletion of Ascl1 in cortical progenitors or OPCs, mouse focal demyelination model, lineage tracing, immunohistochemistry The Journal of neuroscience High 23739972
2022 ASCL1 acts as a driver of neuroendocrine/neuronal lineage transcriptional programs in prostate cancer through large-scale chromatin remodeling; ASCL1 motif is enriched in hyper-accessible regions after androgen receptor pathway inhibitor treatment, and targeting ASCL1 switches neuroendocrine lineage back to luminal epithelial state via disruption of PRC2 through UHRF1/AMPK axis. ATAC-seq, ChIP-seq, ASCL1 knockdown, UHRF1/AMPK pathway inhibition, chromatin architecture analysis in prostate cancer cells Nature communications High 35477723
2015 EZH2 promotes SCLC progression by epigenetically silencing TβRII expression, suppressing TGF-β signaling; ASCL1 is a Smad-dependent TGF-β target gene that promotes survival in SCLC cells, and EZH2 promotes SCLC by suppressing the TGF-β-Smad-ASCL1 pathway. TβRII overexpression in SCLC cells, EZH2 inhibition, Smad pathway activation, in vitro cell growth and in vivo tumor formation assays Cell discovery Medium 27462425
2014 EWS-WT1 fusion oncoprotein directly activates ASCL1 transcription by binding the proximal ASCL1 promoter through multiple WT1-responsive elements, inducing neural gene expression and partial neural differentiation. Transgenic mouse model, ChIP for EWS-WT1 at ASCL1 promoter, reporter assays with WT1-responsive element mutations, EWS-WT1 siRNA knockdown Cancer research Medium 24934812
2021 ASCL1 in SCLC represses a SOX9+ mesenchymal/neural crest stem-like state; ASCL1 is critical for expression of NKX2-1, FOXA2, and INSM1 and represses SOX9/RUNX1/RUNX2 program in vivo; genetic depletion of ASCL1 promotes emergence of osteosarcoma and chondroid tumors and inhibits tumor initiation in MYC-driven SCLC. Genetically engineered mouse models with conditional Ascl1 deletion, RNA-seq, ChIP-seq, tumor histology Genes & development High 34016693
2019 ASCL1 is a MYCN- and LMO1-dependent member of the adrenergic neuroblastoma core regulatory circuitry; regulatory elements controlling ASCL1 are bound by LMO1, MYCN, GATA3, HAND2, PHOX2B, TBX2 and ISL1; ASCL1 and LMO1 directly regulate CRC gene expression, and ASCL1 is required for neuroblastoma cell growth and arrest of differentiation. ChIP-seq, RNA-seq, ASCL1 knockdown in neuroblastoma cells, promoter/enhancer analysis Nature communications High 31819055
2023 Endogenous ASCL1 functions both as a classical pioneer factor (binding closed chromatin) and as a non-pioneer remodeler (binding permissive chromatin to induce conformation changes) during human neural differentiation; ASCL1 interacts with BAF SWI/SNF chromatin remodeling complexes, primarily at non-pioneer targets, with codependent DNA binding and remodeling at a subset of ASCL1/SWI/SNF co-targets. Single-cell RNA-seq, ASCL1 knockout model, ATAC-seq, ChIP-seq, Co-IP for ASCL1-SWI/SNF interaction, chromatin conformation assays Genes & development High 36931659
2021 Ascl1-mediated astrocyte-to-neuron conversion directly activates 107 target genes; among direct ASCL1 targets, Klf10 regulates neuritogenesis, Myt1 and Myt1l are critical for electrophysiological maturation of induced neurons, and Neurod4 and Chd7 are required for efficient conversion. RNA-seq, ChIP-seq during astrocyte-to-neuron reprogramming, siRNA knockdown of individual ASCL1 targets, functional electrophysiology assays Stem cell reports High 33577795
2018 ASCL1 is ubiquitylated on lysines within the bHLH domain in the cytoplasm by the E3 ligase Huwe1, targeting it for degradation; chromatin-bound ASCL1 associates with short ubiquitin chains that do not target it for destruction, occurring on lysines in the N-terminal region or bHLH domain independently of Huwe1. Thus subcellular localization controls the type of ubiquitylation and fate of ASCL1. Subcellular fractionation, ubiquitin chain immunoprecipitation, lysine-to-arginine mutagenesis, Huwe1 knockdown, proteasome inhibition experiments Scientific reports High 29545540
2022 ASCL1 is highly phosphorylated on Serine-Proline sites in GBM stem cells; a phosphorylation-resistant form of ASCL1 (cannot be phosphorylated on SP sites) drives GBM cells more efficiently into neuronal lineage and out of cell cycle than wild-type ASCL1; deletion of ID2 further enhances this differentiation block reversal. Phospho-ASCL1 immunoblotting, overexpression of phospho-mutant ASCL1 in GBM stem cells, CRISPR deletion of ID2, cell cycle analysis, differentiation markers Scientific reports Medium 35149717
2020 Injury-induced STAT signaling limits Ascl1-mediated reprogramming of Müller glia into retinal neurons; STAT signaling directs Ascl1 to developmentally inappropriate chromatin targets; pharmacological STAT inhibition combined with Ascl1 expression dramatically increases neuronal generation from Müller glia. Single-cell RNA-seq, Ascl1-ChIPseq, ATAC-seq in Müller glia, STAT inhibitor treatment, transgenic Ascl1 expression Cell reports High 32075759
2020 ASCL1 regulates neurodevelopmental transcription factors and cell cycle genes in GBM; genetic loss of ASCL1 significantly reduces glioma cell proliferation in a mouse glioma model, with RNA-seq revealing downregulation of cell cycle genes upon ASCL1 loss. RNA-seq, conditional Ascl1 deletion in mouse glioma model, survival analysis, cell proliferation assays Glia Medium 32573857
2018 ASCL1 proneural transcription factor governs glioblastoma stem cell proneural subgroup affiliation by directly repressing NDRG1 (a mesenchymal gene); ASCL1 binding to NDRG1 regulatory regions drives a glial-to-neuronal lineage switch while concomitantly suppressing mesenchymal features. ChIP-seq, ASCL1 overexpression/knockdown, NDRG1 silencing, tumor formation assays, gene expression profiling in patient-derived GSCs Cell death and differentiation Medium 30538287
2024 ASCL1 is required for the neuroendocrine lineage transition in prostate cancer; ASCL1+ cells arise from KRT8+ luminal cells in vivo; Ascl1 loss in established NEPC causes transient regression followed by recurrence, but deletion before transplantation abrogates lineage plasticity resulting in castration-sensitive adenocarcinomas. Mouse prostate organoid transplantation model, multiplexed immunofluorescence, spatial transcriptomics, genetic Ascl1 deletion at different tumor stages Nature cancer High 39394434
2024 Ascl1 loss in mouse prostate cancer model does not decrease tumor incidence or growth, but causes notable decrease in neuroendocrine identity and increase in basal-like identity, establishing ASCL1 as required for driving NE differentiation but not overall tumor growth in this context. Prostate organoid allografts from Rb1/Trp53/Myc GEMMs, conditional Ascl1 genetic deletion, IHC/RNA-seq for lineage markers Cancer research Medium 39264686
2020 Gsx2 physically interacts with the bHLH domain of Ascl1 in lateral ganglionic eminence progenitors, interfering with Ascl1's DNA binding and limiting neurogenesis; this Gsx2-Ascl1 interaction is enriched in LGE ventricular zone progenitors, while Ascl1-E-protein (Tcf3) interactions predominate in the subventricular zone. Luciferase/reporter assays, co-immunoprecipitation, DNA-binding assays, proximity ligation assay in tissue sections, conditional misexpression in mouse Development High 32122989
2022 ASCL1 in SCLC regulates super-enhancer-associated miRNAs including miR-7, miR-375, miR-200b-3p, and miR-429 (activating them) and suppresses miR-455-3p; multiple ASCL1-regulated miRNAs combinatorially repress targets including YAP1 (co-targeted by miR-9 and miR-375). CUT&Tag chromatin profiling (H3K27me3, H3K4me3, H3K27ac), ASCL1 knockdown with RNA-seq and miRNA array in SCLC cells Cancer science Medium 35789143
2021 The BAP1/ASXL3/BRD4 epigenetic axis regulates ASCL1-dependent SCLC transcriptional programming; pharmacological inhibition of BAP1 catalytic activity induces ASXL3 degradation, disrupting the BAP1/ASXL3/BRD4 complex at active enhancers and repressing ASCL1/MYCL/E2F neuroendocrine lineage signaling. BAP1 inhibitor (iBAP-II) treatment, Co-IP for BAP1/ASXL3/BRD4 complex, ChIP-seq at enhancers, cell viability and in vivo tumor assays Oncogene Medium 35194152
2000 Notch1 intracellular domain inhibits differentiation of neuroblastoma cells; HES1 binds to an N-box sequence in the HASH-1 (ASCL1) promoter in gel mobility shift assays, and HES1 activation during differentiation contributes to HASH-1 downregulation. Gel mobility shift assay with HES1 protein and ASCL1 N-box oligonucleotide, constitutive Notch1-ICD expression, differentiation assays in neuroblastoma cell lines International journal of cancer Medium 11054669
2018 ASCL1 conditional deletion in NG2-glia of embryonic or adult spinal cord results in significant reduction in proliferation but not differentiation of these cells; WM NG2-glia maintain higher ASCL1 levels than GM NG2-glia, correlating with higher proliferative capacity; ASCL1+ OLP clones are primarily restricted to GM or WM compartments. Conditional Ascl1 deletion in NG2-glia, long-term clonal lineage analysis, BrdU/EdU proliferation assays in spinal cord Glia Medium 29683222
2022 In neuroblastoma, ASCL1 maintains rapid proliferation and regulates chromatin accessibility at differentiation gene regulatory regions; ASCL1 deletion compromises the ability of MYC/MYCN and CRC component proteins PHOX2B and GATA3 to bind chromatin, without substantially affecting CRC gene transcript levels. CRISPR deletion of ASCL1 in neuroblastoma cell lines, genome-wide RNA-seq, ATAC-seq, ChIP-seq for PHOX2B/GATA3 binding, proliferation assays Frontiers in cell and developmental biology Medium 36263020
2022 Ascl1, together with Mef2c, drives efficient cardiac reprogramming; MEF2C shifts ASCL1 chromatin binding away from neuronal gene targets toward cardiac gene targets, demonstrating cross-lineage pioneer factor activity dependent on partner transcription factor context. ChIP-seq, RNA-seq during cardiac reprogramming, MEF2C co-expression with ASCL1, comparison to neuronal reprogramming regulatome Cell stem cell Medium 36206732
2013 Loss of Ascl1 in mouse dorsal horn specifically eliminates late-born inhibitory interneurons; Ascl1-dependent inhibitory interneurons expressing pDyn, Kcnip2, and Rorb are key players in nociceptive reflex plasticity. Genome-wide expression profiling of Ascl1-/- spinal dorsal horn, in situ hybridization, isolated spinal cord electrophysiology for nociceptive reflex The Journal of neuroscience Medium 23616538
2024 ASCL1 drives drug tolerance to osimertinib in EGFR-mutant lung cancer by initiating an epithelial-to-mesenchymal gene expression program in permissive cellular contexts. Patient-derived xenograft osimertinib treatment, single-cell transcriptional profiling of residual disease, ASCL1 expression analysis Cancer research Low 38359163

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1998 Localization of ASH1 mRNA particles in living yeast. Molecular cell 1312 9809065
2020 SCLC Subtypes Defined by ASCL1, NEUROD1, POU2F3, and YAP1: A Comprehensive Immunohistochemical and Histopathologic Characterization. Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer 414 33011388
2016 ASCL1 and NEUROD1 Reveal Heterogeneity in Pulmonary Neuroendocrine Tumors and Regulate Distinct Genetic Programs. Cell reports 412 27452466
1998 The Drosophila trithorax group proteins BRM, ASH1 and ASH2 are subunits of distinct protein complexes. Development (Cambridge, England) 239 9735357
2002 Histone methylation by the Drosophila epigenetic transcriptional regulator Ash1. Nature 229 12397363
2004 The histone methyltransferases Trithorax and Ash1 prevent transcriptional silencing by Polycomb group proteins. EMBO reports 207 15031712
2006 RETRACTED: Noncoding RNAs of trithorax response elements recruit Drosophila Ash1 to Ultrabithorax. Science (New York, N.Y.) 177 16497925
2000 The myosin motor, Myo4p, binds Ash1 mRNA via the adapter protein, She3p. Proceedings of the National Academy of Sciences of the United States of America 176 10792032
2000 She2p, a novel RNA-binding protein tethers ASH1 mRNA to the Myo4p myosin motor via She3p. The EMBO journal 168 11032818
1999 Structural elements required for the localization of ASH1 mRNA and of a green fluorescent protein reporter particle in vivo. Current biology : CB 165 10209102
2000 She2p is a novel RNA-binding protein that recruits the Myo4p-She3p complex to ASH1 mRNA. The EMBO journal 164 11101531
2004 A new yeast PUF family protein, Puf6p, represses ASH1 mRNA translation and is required for its localization. Genes & development 151 15198983
2017 ASCL1 Reorganizes Chromatin to Direct Neuronal Fate and Suppress Tumorigenicity of Glioblastoma Stem Cells. Cell stem cell 142 28712938
2019 High Hes1 expression and resultant Ascl1 suppression regulate quiescent vs. active neural stem cells in the adult mouse brain. Genes & development 130 30862661
2007 Trithorax-group protein ASH1 methylates histone H3 lysine 36. Gene 130 17544230
2013 FOXO3 shares common targets with ASCL1 genome-wide and inhibits ASCL1-dependent neurogenesis. Cell reports 126 23891001
2011 miR-375 is activated by ASH1 and inhibits YAP1 in a lineage-dependent manner in lung cancer. Cancer research 123 21856745
2022 ASCL1 activates neuronal stem cell-like lineage programming through remodeling of the chromatin landscape in prostate cancer. Nature communications 117 35477723
2013 Ascl1/Mash1 promotes brain oligodendrogenesis during myelination and remyelination. The Journal of neuroscience : the official journal of the Society for Neuroscience 116 23739972
2005 Stable incorporation of sequence specific repressors Ash1 and Ume6 into the Rpd3L complex. Biochimica et biophysica acta 115 16314178
1996 The Drosophila ash1 gene product, which is localized at specific sites on polytene chromosomes, contains a SET domain and a PHD finger. Genetics 114 8725238
2012 Histone methyltransferase ASH1 orchestrates fibrogenic gene transcription during myofibroblast transdifferentiation. Hepatology (Baltimore, Md.) 108 22488473
2007 Local activation of yeast ASH1 mRNA translation through phosphorylation of Khd1p by the casein kinase Yck1p. Molecular cell 100 17588515
2019 Proneural factors Ascl1 and Neurog2 contribute to neuronal subtype identities by establishing distinct chromatin landscapes. Nature neuroscience 99 31086315
2005 Upregulation of ASCL1 and inhibition of Notch signaling pathway characterize progressive astrocytoma. Oncogene 99 16103883
2015 EZH2 promotes progression of small cell lung cancer by suppressing the TGF-β-Smad-ASCL1 pathway. Cell discovery 95 27462425
2009 The ASH1 HOMOLOG 2 (ASHH2) histone H3 methyltransferase is required for ovule and anther development in Arabidopsis. PloS one 94 19915673
2020 STAT Signaling Modifies Ascl1 Chromatin Binding and Limits Neural Regeneration from Muller Glia in Adult Mouse Retina. Cell reports 91 32075759
2002 The Khd1 protein, which has three KH RNA-binding motifs, is required for proper localization of ASH1 mRNA in yeast. The EMBO journal 88 11867544
2008 Translation of ASH1 mRNA is repressed by Puf6p-Fun12p/eIF5B interaction and released by CK2 phosphorylation. Genes & development 87 18413716
2004 hASH1 expression is closely correlated with endocrine phenotype and differentiation extent in pulmonary neuroendocrine tumors. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 81 14657947
2013 The trithorax group proteins Kismet and ASH1 promote H3K36 dimethylation to counteract Polycomb group repression in Drosophila. Development (Cambridge, England) 73 24004944
2019 ASCL1 is a MYCN- and LMO1-dependent member of the adrenergic neuroblastoma core regulatory circuitry. Nature communications 72 31819055
2012 Achaete-scute homologue-1 (ASH1) stimulates migration of lung cancer cells through Cdk5/p35 pathway. Molecular biology of the cell 70 22696682
2014 Transcriptional control of vertebrate neurogenesis by the proneural factor Ascl1. Frontiers in cellular neuroscience 67 25520623
2000 Functional interaction between the coactivator Drosophila CREB-binding protein and ASH1, a member of the trithorax group of chromatin modifiers. Molecular and cellular biology 63 11094082
2021 ASCL1 represses a SOX9+ neural crest stem-like state in small cell lung cancer. Genes & development 62 34016693
2009 Nuclear shuttling of She2p couples ASH1 mRNA localization to its translational repression by recruiting Loc1p and Puf6p. Molecular biology of the cell 59 19244342
1999 Trithorax and ASH1 interact directly and associate with the trithorax group-responsive bxd region of the Ultrabithorax promoter. Molecular and cellular biology 59 10454589
1998 Ash1, a daughter cell-specific protein, is required for pseudohyphal growth of Saccharomyces cerevisiae. Molecular and cellular biology 56 9566907
2004 Daughter-specific repression of Saccharomyces cerevisiae HO: Ash1 is the commander. EMBO reports 55 15459746
2016 miR-124-9-9* potentiates Ascl1-induced reprogramming of cultured Müller glia. Glia 54 26732729
2018 ASH1-catalyzed H3K36 methylation drives gene repression and marks H3K27me2/3-competent chromatin. eLife 53 30468429
2000 Induced neuroblastoma cell differentiation, associated with transient HES-1 activity and reduced HASH-1 expression, is inhibited by Notch1. International journal of cancer 50 11054669
2019 Analysis of DLL3 and ASCL1 in Surgically Resected Small Cell Lung Cancer (HOT1702). The oncologist 48 31068386
2018 The proneural gene ASCL1 governs the transcriptional subgroup affiliation in glioblastoma stem cells by directly repressing the mesenchymal gene NDRG1. Cell death and differentiation 48 30538287
1994 Molecular genetic analysis of the Drosophila melanogaster gene absent, small or homeotic discs1 (ash1). Genetics 48 7982557
2021 ASCL1, NKX2-1, and PROX1 co-regulate subtype-specific genes in small-cell lung cancer. iScience 47 34466783
2017 Mrg15 stimulates Ash1 H3K36 methyltransferase activity and facilitates Ash1 Trithorax group protein function in Drosophila. Nature communications 46 29158494
2008 Nuclear transit of the RNA-binding protein She2 is required for translational control of localized ASH1 mRNA. EMBO reports 46 18566598
2024 The neuroendocrine transition in prostate cancer is dynamic and dependent on ASCL1. Nature cancer 44 39394434
2017 Epigenetic Editing of Ascl1 Gene in Neural Stem Cells by Optogenetics. Scientific reports 43 28181538
2013 ASCL1 and RET expression defines a clinically relevant subgroup of lung adenocarcinoma characterized by neuroendocrine differentiation. Oncogene 43 24037524
2023 Pioneer factor ASCL1 cooperates with the mSWI/SNF complex at distal regulatory elements to regulate human neural differentiation. Genes & development 42 36931659
2017 Molecular architecture and dynamics of ASH1 mRNA recognition by its mRNA-transport complex. Nature structural & molecular biology 40 28092367
2013 Genome-wide expression analysis of Ptf1a- and Ascl1-deficient mice reveals new markers for distinct dorsal horn interneuron populations contributing to nociceptive reflex plasticity. The Journal of neuroscience : the official journal of the Society for Neuroscience 40 23616538
2008 Human ASH1 expression in prostate cancer with neuroendocrine differentiation. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 40 18311112
2002 Quantitative reverse transcription-polymerase chain reaction measurement of HASH1 (ASCL1), a marker for small cell lung carcinomas with neuroendocrine features. Clinical cancer research : an official journal of the American Association for Cancer Research 40 11948117
2021 Molecular Mechanisms Underlying Ascl1-Mediated Astrocyte-to-Neuron Conversion. Stem cell reports 38 33577795
2013 Quantitative in vivo analysis of chromatin binding of Polycomb and Trithorax group proteins reveals retention of ASH1 on mitotic chromatin. Nucleic acids research 38 23580551
2010 Multiple Myo4 motors enhance ASH1 mRNA transport in Saccharomyces cerevisiae. The Journal of cell biology 38 20457760
2000 Self-association of the SET domains of human ALL-1 and of Drosophila TRITHORAX and ASH1 proteins. Oncogene 38 10656681
2020 ASCL1 regulates neurodevelopmental transcription factors and cell cycle genes in brain tumors of glioma mouse models. Glia 37 32573857
2022 Promoters of ASCL1- and NEUROD1-dependent genes are specific targets of lurbinectedin in SCLC cells. EMBO molecular medicine 35 35263037
2020 Developmental changes in the accessible chromatin, transcriptome and Ascl1-binding correlate with the loss in Müller Glial regenerative potential. Scientific reports 35 32788677
2014 EWS-WT1 oncoprotein activates neuronal reprogramming factor ASCL1 and promotes neural differentiation. Cancer research 35 24934812
2019 Ascl1 Regulates Electric Field-Induced Neuronal Differentiation Through PI3K/Akt Pathway. Neuroscience 34 30771509
2003 RNA-protein interactions promote asymmetric sorting of the ASH1 mRNA ribonucleoprotein complex. RNA (New York, N.Y.) 34 14561888
2002 Ash1 protein, an asymmetrically localized transcriptional regulator, controls filamentous growth and virulence of Candida albicans. Molecular and cellular biology 34 12446785
2011 Phorbol-Ester Mediated Suppression of hASH1 Synthesis: Multiple Ways to Keep the Level Down. Frontiers in molecular neuroscience 33 21441980
2022 Cross-lineage potential of Ascl1 uncovered by comparing diverse reprogramming regulatomes. Cell stem cell 32 36206732
2021 Performance of DNA methylation analysis of ASCL1, LHX8, ST6GALNAC5, GHSR, ZIC1 and SST for the triage of HPV-positive women: Results from a Dutch primary HPV-based screening cohort. International journal of cancer 31 34558659
2021 Heterogeneity of neurons reprogrammed from spinal cord astrocytes by the proneural factors Ascl1 and Neurogenin2. Cell reports 29 34289357
2012 Insights into the achaete-scute homolog-1 gene (hASH1) in normal and neoplastic human lung. Lung cancer (Amsterdam, Netherlands) 29 21684625
2022 ASCL1 phosphorylation and ID2 upregulation are roadblocks to glioblastoma stem cell differentiation. Scientific reports 28 35149717
2021 MAPK pathway activation selectively inhibits ASCL1-driven small cell lung cancer. iScience 28 34712921
2018 Subcellular localisation modulates ubiquitylation and degradation of Ascl1. Scientific reports 28 29545540
2013 The BET protein FSH functionally interacts with ASH1 to orchestrate global gene activity in Drosophila. Genome biology 28 23442797
2010 ASCL1 regulates the expression of the CHRNA5/A3/B4 lung cancer susceptibility locus. Molecular cancer research : MCR 28 20124469
2018 An Integrative Analysis of Transcriptome and Epigenome Features of ASCL1-Positive Lung Adenocarcinomas. Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer 27 30121393
2022 Therapeutic targeting of BAP1/ASXL3 sub-complex in ASCL1-dependent small cell lung cancer. Oncogene 26 35194152
2010 A nucleoporin, Nup60p, affects the nuclear and cytoplasmic localization of ASH1 mRNA in S. cerevisiae. RNA (New York, N.Y.) 26 21036941
2024 ASCL1 Drives Tolerance to Osimertinib in EGFR Mutant Lung Cancer in Permissive Cellular Contexts. Cancer research 25 38359163
2024 Neuroendocrine Differentiation in Prostate Cancer Requires ASCL1. Cancer research 25 39264686
2013 Role of Loc1p in assembly and reorganization of nuclear ASH1 messenger ribonucleoprotein particles in yeast. Proceedings of the National Academy of Sciences of the United States of America 24 24324176
2024 Transcription factors ASCL1 and OLIG2 drive glioblastoma initiation and co-regulate tumor cell types and migration. Nature communications 23 39609428
2019 Inhibition of Glioma Development by ASCL1-Mediated Direct Neuronal Reprogramming. Cells 23 31212628
2014 Of social molecules: The interactive assembly of ASH1 mRNA-transport complexes in yeast. RNA biology 23 25482892
2000 Morphometric analysis of CC10-hASH1 transgenic mouse lung: a model for bronchiolization of alveoli and neuroendocrine carcinoma. Experimental lung research 23 11195458
2020 Physical interactions between Gsx2 and Ascl1 balance progenitor expansion versus neurogenesis in the mouse lateral ganglionic eminence. Development (Cambridge, England) 22 32122989
2005 Genetic association analyses of PHOX2B and ASCL1 in neuropsychiatric disorders: evidence for association of ASCL1 with Parkinson's disease. Human genetics 22 16021468
2022 Helicobacter pylori infection activates Wnt/β-catenin pathway to promote the occurrence of gastritis by upregulating ASCL1 and AQP5. Cell death discovery 21 35538066
2022 The proneural transcription factor ASCL1 regulates cell proliferation and primes for differentiation in neuroblastoma. Frontiers in cell and developmental biology 21 36263020
2018 Instructing neuronal identity during CNS development and astroglial-lineage reprogramming: Roles of NEUROG2 and ASCL1. Brain research 21 29510143
2013 Heterochronic misexpression of Ascl1 in the Atoh7 retinal cell lineage blocks cell cycle exit. Molecular and cellular neurosciences 21 23481413
2004 Human achaete-scute homologue (hASH1) mRNA level as a diagnostic marker to distinguish esthesioneuroblastoma from poorly differentiated tumors arising in the sinonasal tract. American journal of clinical pathology 21 15272537
2023 The ASH1-PEX16 regulatory pathway controls peroxisome biogenesis for appressorium-mediated insect infection by a fungal pathogen. Proceedings of the National Academy of Sciences of the United States of America 20 36649415
2022 Histone H3.3 K27M chromatin functions implicate a network of neurodevelopmental factors including ASCL1 and NEUROD1 in DIPG. Epigenetics & chromatin 20 35590427
2022 ASCL1 regulates super-enhancer-associated miRNAs to define molecular subtypes of small cell lung cancer. Cancer science 20 35789143
2018 ASCL1 regulates proliferation of NG2-glia in the embryonic and adult spinal cord. Glia 19 29683222