ArticleMolecular and cellular biology2014
Yin Yang 1 is a repressor of glutamate transporter EAAT2, and it mediates manganese-induced decrease of EAAT2 expression in astrocytes.
Article in Molecular and cellular biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers, 1 of them a synthesis that pooled it.
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Who cites it
66 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Integrated multi-cohort transcriptional meta-analysis of neurodegenerative diseases.Acta neuropathologica communications · 2014Pooled it
- Functional and Transcriptional Downregulation of Glutamate Transporters (EAAT1 and EAAT2) via DNMT3B Overexpression in Glial Cells.Molecular neurobiology · 2026Article
- FOXO family and neurodegenerative diseases: Mechanisms of action and therapeutic potential.Redox biology · 2026Review
- Environmental Factors Drive Neurodegenerative Diseases Through Glutamate Excitotoxicity: A Convergent Mechanistic Pathway.Neuroscience bulletin · 2026Review
- Defective Astrocyte Maturation Drives Cerebellar Neuroinflammation and Degeneration.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- The Role of Epigenetics in Manganese Neurotoxicity: An Update with a Focus on Non-Coding RNAs and Histone Modifications.Neurochemical research · 2025Review
- Role of dopaminergic RE1-silencing transcription factor (REST) in manganese-induced behavioral deficits and dysregulating dopaminergic and serotonergic neurotransmission in mice.Neurotoxicology · 2025Article
- Yin Yang 1: Function, Mechanisms, and Glia.Neurochemical research · 2025Review
- Microbiota-gut-brain Axis: Novel Potential Pathways for Developing Antiepileptogenic Drugs.Current neuropharmacology · 2025Review
- Gut to brain: essential micronutrient and trace element manganese transport, function and toxicity.Frontiers in physiology · 2025Review
- Excitotoxic Storms of Ischemic Stroke: A Non-neuronal Perspective.Molecular neurobiology · 2024Review
- Histone deacetylase as emerging pharmacological therapeutic target for neuropathic pain: From epigenetic to selective drugs.CNS neuroscience & therapeutics · 2024Review
- Regulation of PD-L1 Expression by YY1 in Cancer: Therapeutic Efficacy of Targeting YY1.Cancers · 2024Review
- Targeting Reactive Astrocytes in Vascular Dementia: Investigation of Neuronal-Astrocyte-Vascular Interactions.Neuroscience insights · 2024Article
- Mutant GGGGCC RNA prevents YY1 from binding to Fuzzy promoter which stimulates Wnt/β-catenin pathway in C9ALS/FTD.Nature communications · 2023Article
- Consequences of Disturbing Manganese Homeostasis.International journal of molecular sciences · 2023Review
- Article
- Cellular Pathogenesis of Hepatic Encephalopathy: An Update.Biomolecules · 2023Review
- Article
- Novel EAAT2 activators improve motor and cognitive impairment in a transgenic model of Huntington's disease.Frontiers in behavioral neuroscience · 2023Article
6 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors.
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Abstract
Impairment of astrocytic glutamate transporter (GLT-1; EAAT2) function is associated with multiple neurodegenerative diseases, including Parkinson's disease (PD) and manganism, the latter being induced by chronic exposure to high levels of manganese (Mn). Mn decreases EAAT2 promoter activity and mRNA and protein levels, but the molecular mechanism of Mn-induced EAAT2 repression at the transcriptional level has yet to be elucidated. We reveal that transcription factor Yin Yang 1 (YY1) is critical in repressing EAAT2 and mediates the effects of negative regulators, such as Mn and tumor necrosis factor alpha (TNF-α), on EAAT2. YY1 overexpression in astrocytes reduced EAAT2 promoter activity, while YY1 knockdown or mutation of the YY1 consensus site of the EAAT2 promoter increased its promoter activity and attenuated the Mn-induced repression of EAAT2. Mn increased YY1 promoter activity and mRNA and protein levels via NF-κB activation. This led to increased YY1 binding to the EAAT2 promoter region. Epigenetically, histone deacetylase (HDAC) classes I and II served as corepressors of YY1, and, accordingly, HDAC inhibitors increased EAAT2 promoter activity and reversed the Mn-induced repression of EAAT2 promoter activity. Taken together, our findings suggest that YY1, with HDACs as corepressors, is a critical negative transcriptional regulator of EAAT2 and mediates Mn-induced EAAT2 repression.
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