H2A.Z Regulates Astrocyte Proliferation and Differentiation via H3K56ac Modification. Mus musculus

Purpose:To gain a deeper insight into how H2A.Z regulates astrocytogenesis, RNA-sequencing (RNA-seq) was performed to analyze the genome-wide changes by H2AZ deletion at E16. Methods: Total RNA was extracted from E16 telencephalic tissue of H2A.ZcKO and H2A.Zfl/fl mice. Then total RNA was quality controlled and quantified using an Agilent 2100 Bioanalyzer. After converting to cDNA and building library, high-throughput sequencing was performed using the Illumina HiSeq 2500 platform in Annoroad Genomics. Results: Approximately approximately one thousand transcripts showed differential expression between the H2A.Zfl/fl and H2A.ZcKO brain, with a fold change ≥1.5 and p value <0.05. Gene ontology (GO) analysis showed that the down-regulated genes were enriched in the terms related to regulation of glial cell differentiation and forebrain development, and cerebellum development. Up-regulated genes showed a significant enrichment of terms involved in negative regulation of cell differentiation. These results reflected the importance of H2A.Z in cortical development. Conclusions: We conclude that RNA-seq based transcriptome characterization would provide a framework for understanding how H2A.Z gene contribute to cortical development. Overall design: Total RNA was extracted from E16 telencephalic tissue of H2A.ZcKO and H2A.Zfl/fl mice and generated by deep sequencing, in triplicate, using Illumina HiSeq 2500.