ArticlePloS one2014
Runx1t1 (Runt-related transcription factor 1; translocated to, 1) epigenetically regulates the proliferation and nitric oxide production of microglia.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 20 citations in OpenAlex.
- Bioinformatic Analysis of Recurrent Genomic Alterations and Corresponding Pathway Alterations in Ewing Sarcoma.Journal of personalized medicine · 2023Article
- Endothelial Cell Response in Kawasaki Disease and Multisystem Inflammatory Syndrome in Children.International journal of molecular sciences · 2023Article
- Checkpoint Kinase 1 (CHK1) Functions as Both a Diagnostic Marker and a Regulator of Epithelial-to-Mesenchymal Transition (EMT) in Triple-Negative Breast Cancer.Current issues in molecular biology · 2022Article
- RUNX1T1 function in cell fate.Stem cell research & therapy · 2022Review
- Transcriptional and epigenetic regulation of microglia in maintenance of brain homeostasis and neurodegeneration.Frontiers in molecular neuroscience · 2022Review
- Identification of RUNX1T1 as a potential epigenetic modifier in small-cell lung cancer.Molecular oncology · 2021Article
- Preclinical and clinical progress for HDAC as a putative target for epigenetic remodeling and functionality of immune cells.International journal of biological sciences · 2021Review
- HDAC Inhibitor Sodium Butyrate-Mediated Epigenetic Regulation Enhances Neuroprotective Function of Microglia During Ischemic Stroke.Molecular neurobiology · 2017Article
- Endothelial angiogenesis is directed by RUNX1T1-regulated VEGFA, BMP4 and TGF-β2 expression.PloS one · 2017Article
- Substance P enhances microglial density in the substantia nigra through neurokinin-1 receptor/NADPH oxidase-mediated chemotaxis in mice.Clinical science (London, England : 1979) · 2015Article
- FTO influences adipogenesis by regulating mitotic clonal expansion.Nature communications · 2015Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMicroglia, the resident immune cells of the brain, undergo rapid proliferation and produce several proinflammatory molecules and nitric oxide (NO) when activated in neuropathological conditions. Runx1t1 (Runt-related transcription factor 1, translocated to 1) has been implicated in recruiting histone deacetylases (HDACs) for transcriptional repression, thereby regulating cell proliferation. In the present study, Runx1t1 expression was shown to localize in amoeboid microglial cells of the postnatal rat brain, being hardly detectable in ramified microglia of the adult brain. Moreover, a marked expression of Runx1t1was induced and translocated to nuclei in activated microglia in vitro and in vivo. In view of these findings, it was hypothesized that Runx1t1 regulates microglial functions during development and in neuropathological conditions. METHODS AND
findingssiRNA-mediated knockdown of Runx1t1 significantly decreased the expression level of cell cycle-related gene, cyclin-dependent kinase 4 (Cdk4) and proliferation index in activated BV2 microglia. It was also shown that HDAC inhibitor (HDACi) treatment mimics the effects of Runx1t1 knockdown on microglial proliferation, confirming that microglial proliferation is associated with Runx1t1 expression and HDACs activity. Further, Runx1t1 and HDACs were shown to promote neurotoxic effect of microglia by repressing expression of LAT2, L-aminoacid transporter-2 (cationic amino acid transporter, y+ system), which normally inhibits NO production. This was confirmed by chromatin immunoprecipitation (ChIP) assay, which revealed that Runx1t1 binds to the promoter region of LAT2 and this binding increased upon microglial activation. However, the enhanced binding of Runx1t1 to the LAT2 promoter could not repress the LAT2 expression when the BV2 microglia cells were treated with HDACi, indicating that Runx1t1 requires HDACs to transcriptionally repress the expression of LAT2. CONCLUSION/
interpretationIn conclusion, it is suggested that Runx1t1 controls proliferation and the neurotoxic effect of microglia by epigenetically regulating Cdk4 and LAT2 via its interaction with HDACs.
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