hide
Free keywords:
Zac1, Cell fate decisions, Neural stem cells, Genomic imprinting, Igf2-H19, Dlk1, p57Kip2, Necdin, Differentiation, Imprinted gene networks
Abstract:
Neural stem cells (NSCs) and imprinted genes play an important role in
brain development. On historical grounds, these two determinants have
been largely studied independently of each other. Recent evidence
suggests, however, that NSCs can reset select genomic imprints to
prevent precocious depletion of the stem cell reservoir. Moreover,
imprinted genes like the transcriptional regulator Zac1 can fine tune
neuronal vs astroglial differentiation of NSCs. Zac1 binds in a
sequence-specific manner to pro-neuronal and imprinted genes to confer
transcriptional regulation and furthermore coregulates members of the
p53-family in NSCs. At the genome scale, Zac1 is a central hub of an
imprinted gene network comprising genes with an important role for NSC
quiescence, proliferation and differentiation. Overall, transcriptional,
epigenomic, and genomic mechanisms seem to coordinate the functional
relationships of NSCs and imprinted genes from development to
maturation, and possibly aging.
