Role of the histone methyltransferases Ezh2 and Suv4-20h1/Suv4-20h2 in neurogenesis

Abstract

Mechanisms regulating neurogenesis involve broad and complex processes that represent intriguing therapeutic targets in the field of regenerative medicine. One influential factor guiding neural stem cell proliferation and cellular differentiation during neurogenesis are epigenetic mechanisms. We present an overview of epigenetic mechanisms including chromatin structure and histone modifications; and discuss novel roles of two histone modifiers, Ezh2 and Suv4-20h1/Suv4-20h2 (collectively referred to as Suv4-20h), in neurodevelopment and neurogenesis. This review will focus on broadly reviewing epigenetic regulatory components, the roles of epigenetic components during neurogenesis, and potential applications in regenerative medicine.

Keywords: Ezh2; Suv4-20h; adult neurogenesis; epigenetic; histone co-regulation; histone modification; neurodevelopment; neurogenesis; regenerative medicine.

Figure 1

Neural cell fate regulation by histone modifiers Ezh2 and Suv4-20h. Ezh2 and Suv4-20h co-regulate neural cell fate decisions within Gfap positive Radial glial-like cells. Loss of both Ezh2 and Suv4-20h results in disruption of neural cell fate and a dramatic defect in hippocampal development (Chang et al., 2022). Such a change in cell fate was not observed in single knockouts of Ezh2 or Suv4-20h within the developing hippocampus. In the adult hippocampus, Ezh2 and Suv4-20h perform distinct roles within neural stem progenitor cells (Rhodes et al., 2018). In such a scenario, Ezh2 inhibits lineage commitment and differentiation, while Suv4-20h regulates the cell cycle in mitotic neural progenitors, ultimately regulating the rate of neurogenesis and neural cell fate. RGL: Radial glial-like. Unpublished data.