Regulatory elements with preferential activity in cortical interneurons identified by histone modification ChIP-seq

Cortical interneuron (CIN) dysfunction is thought to play a major role in neuropsychiatric conditions like epilepsy, schizophrenia and autism. It is therefore essential to understand how the development, physiology and functions of CINs influence cortical circuit activity and behavior in model organisms such as mice and primates. We sought to discover gene regulatory enhancer elements (REs) that can be used in AAV viral vectors to drive expression in CINs through systematic genome-wide identification of putative REs (pREs) that are preferentially active in immature CINs by histone modification ChIP-seq. We evaluated two novel pREs in AAV vectors, alongside the well-established Dlx I12b enhancer, and found that they drove CIN-specific reporter expression in adult mice. FAC-sorted GFP-positive CINs and GFP-negative non-CINs from microdissected cerebral cortical tissue from P2 Gad67-GFP mice were used in histone modification ChIP-seq experiments. We performed two independent replicate experiments with antibodies against H3K27ac and H3K27me3 with matched input controls.