Abstract
In specific regions of the adult mammalian brain, neural stem cells (NSCs) generate new neurons throughout life. Emerging evidence indicate that chromatin-based transcriptional regulation is a key epigenetic mechanism for the life-long function of adult NSCs. In the adult mouse brain, NSCs in the subventricular zone (SVZ) retain the ability to produce both neurons and glia for the life of the animal. In this review, we discuss the origin and function of SVZ NSCs as they relate to key epigenetic concepts of development and potential underlying mechanism of chromatin-based transcriptional regulation. A central point of discussion is how SVZ NSCs – which possess many characteristics of mature, non-neurogenic astrocytes – maintain a “youthful” ability to produce both neuronal and glial lineages. In addition to reviewing data regarding the function of chromatin-modifying factors in SVZ neurogenesis, we incorporate our growing understanding that long non-coding RNAs serve as an important element to chromatin-based transcriptional regulation, including that of SVZ NSCs. Discoveries regarding the epigenetic mechanisms of adult SVZ NSCs may provide key insights into fundamental principles of adult stem cell biology as well as the more complex and dynamic developmental environment of the embryonic brain.
Highlights
While the vast majority of neurons in the adult mammalian brain arise during embryonic development, in specific brain regions, new neurons are born continuously throughout life
Do type B1 cells epigenetically “preserve” the neurogenic potential of their radial glial origin? What epigenetic mechanisms are required for the establishment and maintenance of adult neural stem cells (NSCs)? We review aspects of radial glial biology that support, on a conceptual level, the notion that cell-intrinsic epigenetic mechanisms play a critical role in the development and long-term neurogenic function of subventricular zone (SVZ) type B1 cells
Based on the above mentioned findings describing a role for long non-coding RNAs (lncRNAs) in targeting mixed lineage leukemia (MLL) complexes to Hox genes for positive transcriptional regulation, it is tempting to speculate that the localization of MLL1 to Dlx1/2 regulatory elements requires Dlx1as, or other lncRNAs
Summary
While the vast majority of neurons in the adult mammalian brain arise during embryonic development, in specific brain regions, new neurons are born continuously throughout life. POLYCOMB GROUP AND TRITHORAX GROUP CHROMATIN-MODIFYING FACTORS: CRITICAL REGULATORS OF ADULT SVZ NEUROGENESIS The polycomb group (PcG) and trithorax group (trxG) gene products, originally described in Drosophila, repress or activate transcription, respectively, to control the specification and maintenance of cell identity.
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