ArticleBMC genomics2022
Elevated ASCL1 activity creates de novo regulatory elements associated with neuronal differentiation.
Article in BMC genomics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
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Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 39 citations in OpenAlex.
- Extended genome-wide association study employing the African genome resources panel identifies novel susceptibility loci for Alzheimer's disease in individuals of African ancestry.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Pooled it
- Comparative ASCL1 Interactome Analysis Reveals CDK2-Cyclin A2 as Suppressors of Differentiation in MYCN-Amplified Neuroblastoma.Molecular cancer research : MCR · 2026Article
- ASCL1 promotes nuclear shrinkage in transdifferentiation by suppressing NUP37.Stem cell reports · 2026Article
- Eukaryote initiation factor 6 modulates small-cell lung carcinoma plasticity via the integrin-FAK signaling axis.Nature communications · 2026Article
- A conserved differentiation programme facilitates inhibitory neuron production in the developing mouse and human cerebellum.Development (Cambridge, England) · 2025Article
- Neocortical neurogenesis: a proneural gene perspective.The FEBS journal · 2025Review
- Chromatin-dependent motif syntax defines differentiation trajectories.Molecular cell · 2025Article
- Distinct proliferative and neuronal programmes of chromatin binding and gene activation by ASCL1 are cell cycle stage-specific.Development (Cambridge, England) · 2025Article
- Cell fate acquisition and reprogramming by the proneural transcription factor ASCL1.Open biology · 2025Review
- Effect of Glutamate Antibodies on ASCL1 Gene Expression in Aging Mice with Spatial Memory Impairment Caused by Amyloid Fibrils of the Proinflammatory Protein S100A9.Bulletin of experimental biology and medicine · 2025Article
- The chemotherapy agent doxorubicin induces CNS expression of Ascl1, a regulator of adult neurogenesis and differentiation.Scientific reports · 2025Article
- Phospho-regulation of ASCL1-mediated chromatin opening during cellular reprogramming.Development (Cambridge, England) · 2024Article
- Therapeutic Exploitation of Neuroendocrine Transdifferentiation Drivers in Prostate Cancer.Cells · 2024Review
- Reprogramming astroglia into neurons with hallmarks of fast-spiking parvalbumin-positive interneurons by phospho-site-deficient Ascl1.Science advances · 2024Article
- Maternal gut Bifidobacterium breve modifies fetal brain metabolism in germ-free mice.Molecular metabolism · 2024Article
- Direct neuronal reprogramming of mouse astrocytes is associated with multiscale epigenome remodeling and requires Yy1.Nature neuroscience · 2024Article
- Article
- Pioneer factors: roles and their regulation in development.Trends in genetics : TIG · 2024Review
- Generation of an inducible dCas9-SAM human PSC line for endogenous gene activation.Frontiers in cell and developmental biology · 2024Article
- ASCL1 promotes Scrt2 expression in the neural tube.Frontiers in cell and developmental biology · 2024Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundThe pro-neural transcription factor ASCL1 is a master regulator of neurogenesis and a key factor necessary for the reprogramming of permissive cell types to neurons. Endogenously, ASCL1 expression is often associated with neuroblast stem-ness. Moreover, ASCL1-mediated reprogramming of fibroblasts to differentiated neurons is commonly achieved using artificially high levels of ASCL1 protein, where ASCL1 acts as an "on-target" pioneer factor. However, the genome-wide effects of enhancing ASCL1 activity in a permissive neurogenic environment has not been thoroughly investigated. Here, we overexpressed ASCL1 in the neuronally-permissive context of neuroblastoma (NB) cells where modest endogenous ASCL1 supports the neuroblast programme.
resultsIncreasing ASCL1 in neuroblastoma cells both enhances binding at existing ASCL1 sites and also leads to creation of numerous additional, lower affinity binding sites. These extensive genome-wide changes in ASCL1 binding result in significant reprogramming of the NB transcriptome, redirecting it from a proliferative neuroblastic state towards one favouring neuronal differentiation. Mechanistically, ASCL1-mediated cell cycle exit and differentiation can be increased further by preventing its multi-site phosphorylation, which is associated with additional changes in genome-wide binding and gene activation profiles.
conclusionsOur findings show that enhancing ASCL1 activity in a neurogenic environment both increases binding at endogenous ASCL1 sites and also results in additional binding to new low affinity sites that favours neuronal differentiation over the proliferating neuroblast programme supported by the endogenous protein. These findings have important implications for controlling processes of neurogenesis in cancer and cellular reprogramming.
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