Examining the Potential Role of Transcription Factors and Chromatin State in Ion Channel Gene Expression During Neurodevelopment in the Murine Neocortex
The requirement for ion channel gene expression differs between the prenatal and postnatalperiod within the brain. In the adult brain ion channel gene usage is critical for mature electrical firing, which requires the coordinated expression of multiple ion channel genes to orchestrate the unique firing of a particular cell type. However, during development, before mature electrical signaling is initiated, tight regulation of ion channel gene expression level and timing is critical for the mature firing pattern as well as neuronal development and cortical formation. To achieve both of these goals ion channels need to be regulated during prenatal development, but potentially primed to allow for postnatal expression and mature firing. This implies that there is a requirement for a complex and dynamic mechanism for gene regulation, which has not yet been understood in the field. Our preliminary work has demonstrated that this regulation may involve the repression of ion channel genes prenatally via H3K27me3, which is subsequently removed postnatally to allow for expression. Building on this work, we examined the potential regulation of putative regulatory elements repressed by H3K27me3 and found transcription factor binding motifs that could control ion channel gene expression in a temporal and gene family specific manner. Then we examined the dynamic activation at these genes with the deposition of H3K4me3 and found that not only does H3K4me3 increase in the postnatal period as expected with postnatal repression, but it is also enriched similarly to H3K27me3 in the prenatal period. This could mean these regions are regulated in a bivalent manner with H3K4me3 priming the repressed genes prenatally for postnatal expression, demonstrating the necessary dynamic gene expression ion channel genes need.