Single cell ATAC-seq analysis in mouse embryonic medial ganglionic eminence (MGE) under deletion of Ezh2 gene (10X Genomics Multiome)

Enhancer of zeste homolog 2 (Ezh2) is the methyltransferase component of the Polycomb Repressive Complex 2 (PRC2), which is critical for trimethylation of histone 3 at lysine 27 (H3K27me3) and results in gene repression. Mutations in EZH2 and dysregulation of H3K27me3 can lead to neurodevelopmental abnormalities such as Weaver Syndrome and ataxia-telangiectasia. During cortical neurogenesis, H3K27me3 is a critical epigenetic modification that regulates cellular maturation rate, and in turn, determines when precursor cells exit the cell cycle. Loss of function studies reveal that Ezh2 plays a critical role in epigenetic regulation of neuronal fate and maturation in some brain regions, but a role for Ezh2 in forebrain GABAergic interneurons has not been explored. Here, we removed Ezh2 from the medial ganglionic eminence (MGE) to study its role in interneuron development. WT, Het, and Ezh2 KO mice (Nkx2.1-CreC/+;Ezh2;Ai9F/+) were created by Nkx2.1-CreC/C;Ezh2F/+ males crossed to Ai9F/F;Ezh2F/+ females. Single nuclei from embryonic day 12.5 (e12) and 15.5 (e15) from each genotype were prepared to analyze chromatin accessibility using 10X Genomics Multiome pipeline.