PT  - JOURNAL ARTICLE
AU  - Giulia Gaudenzi
AU  - Olga Dethlefsen
AU  - Julian Walfridsson
AU  - Ola Hermanson
TI  - Pax6 and KDM5C co-occupy a subset of developmentally critical genes including Notch signaling regulators in neural progenitors
AID  - 10.1101/579219
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 579219
4099  - http://biorxiv.org/content/early/2019/03/16/579219.short
4100  - http://biorxiv.org/content/early/2019/03/16/579219.full
AB  - Pax6 is a key transcription factor in neural development. While generally viewed as a transcriptional activator, mechanisms underlying Pax6 function as a repressor is less well understood. Here we show that Pax6 acts as a direct repressor of transcription associated with a decrease in H3K4me3 levels. Genome wide analysis of the co-occupancy of the H3K4 demethylase KDM5C and Pax6 with 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 HES1 mRNA levels, differences that could be due to gene-specific variations in the chromatin landscape. Our findings suggest that PAX6 and KDM5C co-regulate a subset of genes implicated in brain development, including members of the Notch signaling family.