Tet2-mediated epigenetic drive for astrocyte differentiation from embryonic neural stem cells
Open Access
- 29 April 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Cell Death Discovery
- Vol. 6 (1), 1-12
- https://doi.org/10.1038/s41420-020-0264-5
Abstract
DNA methylation and demethylation at CpG di-nucleotide sites plays important roles in cell fate specification of neural stem cells (NSCs). We have previously reported that DNA methyltransferases, Dnmt1and Dnmt3a, serve to suppress precocious astrocyte differentiation from NSCs via methylation of astroglial lineage genes. However, whether active DNA demethylase also participates in astrogliogenesis remains undetermined. In this study, we discovered that a Ten-eleven translocation (Tet) protein, Tet2, which was critically involved in active DNA demethylation through oxidation of 5-Methylcytosine (5mC), drove astrocyte differentiation from NSCs by demethylation of astroglial lineage genes including Gfap. Moreover, we found that an NSC-specific bHLH transcription factor Olig2 was an upstream inhibitor for Tet2 expression through direct association with the Tet2 promoter, and indirectly inhibited astrocyte differentiation. Our research not only revealed a brand-new function of Tet2 to promote NSC differentiation into astrocytes, but also a novel mechanism for Olig2 to inhibit astrocyte formation.This publication has 45 references indexed in Scilit:
- Enzymatic Analysis of Tet Proteins: Key Enzymes in the Metabolism of DNA MethylationMethods in Enzymology, 2012
- Tet Proteins Can Convert 5-Methylcytosine to 5-Formylcytosine and 5-CarboxylcytosineScience, 2011
- Identification of novel transcripts in annotated genomes using RNA-SeqBioinformatics, 2011
- Using MACS to Identify Peaks from ChIP‐Seq DataCurrent Protocols in Bioinformatics, 2011
- A novel bioinformatics pipeline for identification and characterization of fusion transcripts in breast cancer and normal cell linesNucleic Acids Research, 2011
- Phosphorylation State of Olig2 Regulates Proliferation of Neural ProgenitorsNeuron, 2011
- Role of Tet proteins in 5mC to 5hmC conversion, ES-cell self-renewal and inner cell mass specificationNature, 2010
- Dnmt3a-Dependent Nonpromoter DNA Methylation Facilitates Transcription of Neurogenic GenesScience, 2010
- CEAS: cis-regulatory element annotation systemBioinformatics, 2009
- The Human Genome Browser at UCSCGenome Research, 2002