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Publication : Distinct and separable roles for EZH2 in neurogenic astroglia.

First Author  Hwang WW Year  2014
Journal  Elife Volume  3
Pages  e02439 PubMed ID  24867641
Mgi Jnum  J:213274 Mgi Id  MGI:5584038
Doi  10.7554/eLife.02439 Citation  Hwang WW, et al. (2014) Distinct and separable roles for EZH2 in neurogenic astroglia. Elife 3:e02439
abstractText  The epigenetic mechanisms that enable specialized astrocytes to retain neurogenic competence throughout adult life are still poorly understood. Here we show that astrocytes that serve as neural stem cells (NSCs) in the adult mouse subventricular zone (SVZ) express the histone methyltransferase EZH2. This Polycomb repressive factor is required for neurogenesis independent of its role in SVZ NSC proliferation, as Ink4a/Arf-deficiency in Ezh2-deleted SVZ NSCs rescues cell proliferation, but neurogenesis remains defective. Olig2 is a direct target of EZH2, and repression of this bHLH transcription factor is critical for neuronal differentiation. Furthermore, Ezh2 prevents the inappropriate activation of genes associated with non-SVZ neuronal subtypes. In the human brain, SVZ cells including local astroglia also express EZH2, correlating with postnatal neurogenesis. Thus, EZH2 is an epigenetic regulator that distinguishes neurogenic SVZ astrocytes, orchestrating distinct and separable aspects of adult stem cell biology, which has important implications for regenerative medicine and oncogenesis.DOI: http://dx.doi.org/10.7554/eLife.02439.001.
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