Gene Ontology annotation through association of InterPro records with GO terms
Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity
Annotation inferences using phylogenetic trees
Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping
Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara
Gene Ontology annotation of human sequence-specific DNA binding transcription factors (DbTFs) based on the TFClass database
Electronic Gene Ontology annotations created by ARBA machine learning models
Combined Automated Annotation using Multiple IEA Methods
HASH-1 and E2-2 are expressed in human neuroblastoma cells and form a functional complex.
-
ASCL1 (HASH-1) interacts with E2-2 (TCF4) in yeast and mammalian cells
-
The HASH-1/E2-2 complex binds E-box sequence CACCTG in vitro
-
The complex transactivates E-box containing reporter constructs
-
E2-2 is a major HASH-1 interacting protein in neuroblastoma cells
Proprotein convertase PACE4 is down-regulated by the basic helix-loop-helix transcription factor hASH-1 and MASH-1.
-
ASCL1 binds to E-box cluster in PACE4 promoter (gel shift assay)
-
ASCL1 overexpression represses PACE4 gene expression
-
ASCL1 functions as a transcriptional repressor for specific targets
Notch signaling induces rapid degradation of achaete-scute homolog 1.
-
Notch1 activation induces rapid degradation of ASCL1 protein
-
ASCL1 degradation is proteasome-dependent and involves ubiquitination
-
E12 dimerization protects ASCL1 from Notch-induced degradation
Activation of the phosphatidylinositol 3-kinase/Akt signaling pathway by retinoic acid is required for neural differentiation of SH-SY5Y human neuroblastoma cells.
Origin of GABAergic neurons in the human neocortex.
Mechanisms of neuroendocrine differentiation in pulmonary neuroendocrine cells and small cell carcinoma.
Noradrenergic neuronal development is impaired by mutation of the proneural HASH-1 gene in congenital central hypoventilation syndrome (Ondine's curse).
Conservation of the Notch1 signaling pathway in gastrointestinal carcinoid cells.
Achaete-scute homolog-1 linked to remodeling and preneoplasia of pulmonary epithelium.
-
ASCL1 expression confers resistance to apoptosis
-
Knockdown increases apoptosis in lung cancer cells
-
Nuclear localization demonstrated
Cyberian deep research on ASCL1 functional annotation
-
Comprehensive review of ASCL1 as a pioneer transcription factor
-
ASCL1 preferentially binds CAGCTG E-box motif
-
ASCL1 operates through two mechanisms - classical pioneer and mSWI/SNF-dependent
-
Oscillatory ASCL1 expression maintains progenitors; sustained expression drives differentiation
-
ASCL1 is a lineage oncogene in small cell lung cancer
OpenScientist hypothesis run: ASCL1 DNA-binding dimerization mode (homodimer vs E-protein heterodimer)
-
TF / motif / ChIP analysis concluded ASCL1 binds DNA as a functionally obligate class II bHLH heterodimer with class I E-proteins; the IEA GO:0042802 (identical protein binding, implying homodimer) is over-annotated and should be replaced with GO:0046982 (protein heterodimerization activity).
"GO:0042802 should be removed and replaced with GO:0046982 (protein heterodimerization activity)"
Identification of a human achaete-scute homolog highly expressed in neuroendocrine tumors.
-
Human ASCL1 cloned and characterized
-
95% identity with mouse Mash1
-
Highly expressed in neuroendocrine tumors including SCLC
Mammalian achaete-scute homolog 1 is required for the early development of olfactory and autonomic neurons.
-
Mash1-null mice die shortly after birth due to breathing and feeding defects
-
ASCL1 essential for olfactory epithelium, sympathetic, parasympathetic, and enteric ganglia development
-
ASCL1 acts as a determination gene in olfactory system
Direct conversion of fibroblasts to functional neurons by defined factors.
-
ASCL1 with BRN2 and MYT1L directly converts fibroblasts to functional neurons
-
ASCL1 alone sufficient to induce immature iN cells
-
Induced neurons express neuron-specific proteins and form functional synapses
A novel function of the proneural factor Ascl1 in progenitor proliferation identified by genome-wide characterization of its targets.
-
Over 21,000 ASCL1 binding sites mapped genome-wide
-
272 high-confidence direct targets identified
-
ASCL1 directly controls cell cycle genes - unexpected for proneural factor
-
ASCL1 required for normal neural progenitor proliferation
Hierarchical mechanisms for direct reprogramming of fibroblasts to neurons.
-
ASCL1 binds trivalent chromatin signature (H3K9me3, H3K27ac, H3K4me1)
-
ASCL1 acts first to open chromatin, enabling BRN2 binding
-
ASCL1 binding patterns identical alone or with partners
Oscillatory control of factors determining multipotency and fate in mouse neural progenitors.
-
ASCL1 levels oscillate with 2-3 hour period in neural progenitors
-
Oscillation driven by Hes1 repression of ASCL1
-
Oscillatory expression maintains progenitors; sustained expression drives differentiation
ASCL1 is a lineage oncogene providing therapeutic targets for high-grade neuroendocrine lung cancers.
-
ASCL1 is a lineage oncogene in SCLC
-
ASCL1 knockdown induces apoptosis specifically in ASCL1-positive cancer lines
-
BCL2 is a key ASCL1 target in SCLC
-
72-gene ASCL1 signature predicts poor prognosis
Ascl1 Coordinately Regulates Gene Expression and the Chromatin Landscape during Neurogenesis.
-
ASCL1 functions as a pioneer transcription factor
-
ASCL1 binds closed chromatin and initiates chromatin remodeling
-
63% of ASCL1 binding sites at distal enhancers
ASCL1 and NEUROD1 Reveal Heterogeneity in Pulmonary Neuroendocrine Tumors and Regulate Distinct Genetic Programs.
-
SCLC classified into ASCL1-high (75%), NEUROD1-high (15%), and other subtypes
-
ASCL1 and NEUROD1 occupy non-overlapping genomic sites
-
Only ASCL1 (not NEUROD1) required for SCLC tumor formation
-
ASCL1 directly targets MYCL1, RET, SOX2, NFIB
Proneural factors Ascl1 and Neurog2 contribute to neuronal subtype identities by establishing distinct chromatin landscapes.
-
ASCL1 and Neurog2 bind largely non-overlapping genomic sites
-
ASCL1 drives GABAergic and sympathetic neuronal fates
-
Neurog2 promotes glutamatergic and sensory neuronal identities
The phosphorylation status of Ascl1 is a key determinant of neuronal differentiation and maturation in vivo and in vitro.
-
ASCL1 phosphorylated on serine-proline sites by CDK-cyclin complexes
-
Phosphorylated ASCL1 has reduced DNA binding and transcriptional activity
-
Phospho-mutant ASCL1 shows enhanced neuronal induction activity
Ascl1 Is Required for the Development of Specific Neuronal Subtypes in the Enteric Nervous System.
-
All enteric neuronal subtypes derive from ASCL1-expressing progenitors
-
Calbindin, TH, and VIP neurons selectively decreased in Ascl1-knockout
-
Serotonergic neurons form normally
-
Esophageal neurons fail to form entirely
ASCL1 is a MYCN- and LMO1-dependent member of the adrenergic neuroblastoma core regulatory circuitry.
-
ASCL1 is member of core regulatory circuitry in neuroblastoma
-
MYCN directly regulates ASCL1 expression
-
ASCL1 deletion results in slower neuroblastoma growth
Human ASH1 expression in prostate cancer with neuroendocrine differentiation.
Regionally specified human neural progenitor cells derived from the mesencephalon and forebrain undergo increased neurogenesis following overexpression of ASCL1.
Fragment-Based NMR Study of the Conformational Dynamics in the bHLH Transcription Factor Ascl1.
Impact of cytosine methylation on DNA binding specificities of human transcription factors.
A reference map of the human binary protein interactome.
Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
Pioneer factor ASCL1 cooperates with the mSWI/SNF complex at distal regulatory elements to regulate human neural differentiation.
-
ASCL1 has pioneer transcription factor activity
-
Interacts with mSWI/SNF chromatin remodeling complexes (ARID1A, SMARCC1)
-
Binds nucleosomal DNA and remodels chromatin at neuronal enhancers
-
Drives progenitor differentiation into postmitotic neurons
Ascl1 defines sequentially generated lineage-restricted neuronal and oligodendrocyte precursor cells in the spinal cord.
-
Ascl1 is present in progenitors to neurons and oligodendrocytes, but not astrocytes
"We find that Ascl1 is present in progenitors to both neurons and oligodendrocytes, but not astrocytes."
-
Ascl1-null cells have diminished neuronal differentiation capacity
"Ascl1-null cells in the spinal cord have a diminished capacity to undergo neuronal differentiation, with a subset of these cells retaining characteristics of immature glial cells."