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. Overall design: 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.