RRC ID 70348
Author Shimizu Y, Kawasaki T.
Title Histone acetyltransferase EP300 regulates the proliferation and differentiation of neural stem cells during adult neurogenesis and regenerative neurogenesis in the zebrafish optic tectum.
Journal Neurosci Lett
Abstract Zebrafish have a greater capacity for adult neurogenesis and brain regeneration than mammals. In the adult zebrafish optic tectum (OT), neuroepithelial-like stem cells (NE) contribute to adult neurogenesis, whereas radial glia (RG) contribute to neuronal regeneration after the stab wound injury. The molecular mechanisms regulated by acetylated histone play important roles in these events; however, the functions of histone acetyltransferase (HAT) require further elucidation. The aim of this study was to study the proliferation and differentiation of neural stem cells (NSCs) following treatment with C646, a HAT EP300 inhibitor, to identify the functions of HAT in adult neurogenesis and neuronal regeneration. C646 treatment decreased acetylation of histone 3 lysine 9 in the adult OT. Under physiological conditions, C646 promoted NE proliferation and generation of newborn neurons. EP300 inhibition promoted RG proliferation but suppressed the generation of newborn neurons after the injury. EP300 inhibition downregulated the Notch target genes her4 and her6, which was correlated with NE and RG proliferation in the adult OT. EP300 inhibition regulates the proliferation and differentiation of NSCs by inhibiting histone acetylation and Notch target genes expression, suggesting that the functions of HAT in neurogenesis are opposite to those of histone deacetylase.
Volume 756
Pages 135978
Published 2021-6-21
DOI 10.1016/j.neulet.2021.135978
PII S0304-3940(21)00356-6
PMID 34023416
MeSH Animals Benzoates / pharmacology Cell Proliferation / drug effects Cell Proliferation / physiology* Ependymoglial Cells / cytology Ependymoglial Cells / drug effects Ependymoglial Cells / metabolism Histone Acetyltransferases / metabolism* Neural Stem Cells / cytology Neural Stem Cells / drug effects Neural Stem Cells / metabolism* Neurogenesis / drug effects Neurogenesis / physiology* Nitrobenzenes / pharmacology Pyrazolones / pharmacology Superior Colliculi / cytology Superior Colliculi / drug effects Superior Colliculi / metabolism* Zebrafish
IF 2.274
Zebrafish RIKEN WT