Pax6 and KDM5C co-occupy a subset of developmentally critical genes including Notch signaling regulators in neural progenitors

Pax6is a key transcription factor in neural development. While generally viewed as a transcriptional activator, mechanisms underlying Pax6function as a repressoris less well understood. Here we show that Pax6acts as a direct repressorof transcription associated with a decrease in H3K4me3levels. Genome wide analysis of the co-occupancy of the H3K4 demethylaseKDM5C and Pax6with H3K4me3-negative regions revealed 177 peaks on 131 genes. Specific analysis of these Pax6/KDM5C/ H3K4me3- peaks unveiled a number of genes associated with Notch signaling, including Dll1, Dll4, and Hes1. RNA knockdown of PAX6/KDM5C in human neural progenitors resulted in increased DLL4 gene expression, decreased DLL1 expression, and no significant effect on HES1mRNA levels, differences that could be due to gene-specific variations in the chromatin landscape. Our findings suggest that PAX6and KDM5C co-regulatea subset of genes implicated in brain development, including members of the Notch signaling family.