ArticleCell discovery2015
AF9 promotes hESC neural differentiation through recruiting TET2 to neurodevelopmental gene loci for methylcytosine hydroxylation.
Article in Cell discovery, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 29 citations in OpenAlex.
- Tet2 deficiency orchestrates Alzheimer's pathogenesis through oxidative mtDNA-driven cGAS-STING activation.Journal of neuroinflammation · 2026Article
- Targeting DNA Damage and Repair Pathways in Cerebral Ischemic Stroke: From Bench to Bedside.Translational stroke research · 2026Review
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- Temporally discordant chromatin accessibility and DNA demethylation define short- and long-term enhancer regulation during cell fate specification.Cell reports · 2025Article
- An in vivo CRISPR screen in chick embryos reveals a role for MLLT3 in specification of neural cells from the caudal epiblast.Development (Cambridge, England) · 2025Article
- Mechanisms that regulate the activities of TET proteins.Cellular and molecular life sciences : CMLS · 2022Review
- Multifaceted roles of YEATS domain-containing proteins and novel links to neurological diseases.Cellular and molecular life sciences : CMLS · 2022Review
- Transcription Pause and Escape in Neurodevelopmental Disorders.Frontiers in neuroscience · 2022Review
- Phosphorylation of Tet3 by cdk5 is critical for robust activation of BRN2 during neuronal differentiation.Nucleic acids research · 2020Article
- Derepression of LOXL4 inhibits liver cancer growth by reactivating compromised p53.Cell death and differentiation · 2019Article
- Inferring Regulatory Programs Governing Region Specificity of Neuroepithelial Stem Cells during Early Hindbrain and Spinal Cord Development.Cell systems · 2019Article
- Gene body profiles of 5-hydroxymethylcytosine: potential origin, function and use as a cancer biomarker.Epigenomics · 2018Article
- Suppressing Nodal Signaling Activity Predisposes Ectodermal Differentiation of Epiblast Stem Cells.Stem cell reports · 2018Article
- Epigenetic dysregulation ofOncotarget · 2018Article
- Time-Course Gene Expression Profiling Reveals a Novel Role of Non-Canonical WNT Signaling During Neural Induction.Scientific reports · 2016Article
- Non-catalytic roles for TET1 protein negatively regulating neuronal differentiation through srGAP3 in neuroblastoma cells.Protein & cell · 2016Article
- Epigenetic regulation of early neural fate commitment.Cellular and molecular life sciences : CMLS · 2016Review
- ZNF423 and ZNF521: EBF1 Antagonists of Potential Relevance in B-Lymphoid Malignancies.BioMed research international · 2015Review
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
AF9 mutations have been implicated in human neurodevelopmental diseases and murine Af9 mediates histone methylation during cortical neuron generation. However, AF9 function and related mechanisms in human neurodevelopment remain unknown. Here we show that AF9 is necessary and sufficient for human embryonic stem cell (hESC) neural differentiation and neurodevelopmental gene activation. The 5-methylcytosine (5mC) dioxygenase TET2, which was identified in an AF9-associated protein complex, physically interacted with AF9. Both AF9 and TET2 co-localized in 5-hydroxymethylcytosine (5hmC)-positive hESC-derived neurons and were required for appropriate hESC neural differentiation. Upon binding to AAC-containing motifs, AF9 recruited TET2 to occupy the common neurodevelopmental gene loci to direct 5mC-to-5hmC conversion, which was followed by sequential activation of neural target genes and hESC neural commitment. These findings define an AF9-TET2 regulatory complex for modulating human neural development and reveal a novel mechanism by which the AF9 recognition specificity and TET2 hydroxylation activity cooperate to control neurodevelopmental gene activation.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.