Epigenetic control of neural crest specifier genes by histone demethylases jmjd2A

Abstract

The neural crest (NC) is a multipotent, migratory stem cell‐like population that is able to differentiate in many cell derivatives including the peripheral nervous system and facial skeleton of vertebrate embryos. Many studies have been focused on transcriptional regulation underlying NC formation, but less is known about epigenetic influences. Accordingly, we find unexpectedly dynamic epigenetic modifications are critical for proper temporal control of neural crest gene expression in vivo. The histone demethylase, JumonjiD2a (JmjD2A), is expressed in the forming neural folds and its loss of function using morpholinos causes a dramatic down‐regulation of neural crest specifier genes. Importantly, chromatin immunoprecipitation reveals stage‐specific interactions of JmjD2A with regulatory regions of neural crest genes as well as associated stage‐specific modifications in the methylation states of critical lysine residues. The results clearly show that epigenetic events are important for regulating the chromatin structure on neural crest genes, providing the first in vivo evidence for an epigenetic modification directly controlling a critical developmental event in the vertebrate embryo.Grant Funding Source: USPHS grant HD037105