Like a rolling histone: epigenetic regulation of neural stem cells and brain development by factors controlling histone acetylation and methylation

Abstract

Background: The development of the nervous system is a highly organized process involving the precise and coordinated timing of many complex events. These events require proper expression of genes promoting survival, differentiation, and maturation, but also repression of alternative cell fates and restriction of cell-type-specific gene expression.

Scope of the review: As the enzymes mediating post-translational histone acetylation and methylation are regulating higher order chromatin structure and controlling gene transcription, knowledge of the roles for these enzymes becomes crucial for understanding neural development and disease. The widespread expression and general biological roles for chromatin-modifying factors have hampered the studies of such enzymes in neural development, but in recent years, in vivo and in vitro studies have started to shed light on the various processes these enzymes regulate. In this review we summarize the implications of chromatin-modifying enzymes in neural development, with particular emphasis on enzymes regulating histone acetylation and methylation.

Major conclusions: Enzymes controlling histone acetylation and methylation are involved in the whole process of neural development, from controlling proliferation and undifferentiated, "poised", state of stem cells to promoting and inhibiting neurogenic and gliogenic pathways and neuronal survival as well as neurite outgrowth.

General significance: Aberrant enzymatic activities of histone acetyl transferases, deacetylases, and demethylases have been chemically and genetically associated with neural developmental disorders and cancer. Future studies may aim at linking the genetic and developmental studies to more in-depth biochemical characterization to provide a clearer picture of how to improve the diagnosis, prognosis, and treatment of such disorders. This article is part of a Special Issue entitled Biochemistry of Stem Cells.