Layer-specific chromatin accessibility landscapes reveal regulatory networks in adult mouse visual cortex.

Abstract

Mammalian cortex is a laminar structure, with each layer composed of a characteristic set of cell types with different morphological, electrophysiological, and connectional properties. Here, we define chromatin accessibility landscapes of major, layer-specific excitatory classes of neurons, and compare them to each other and to inhibitory cortical neurons using the Assay for Transposase-Accessible Chromatin with high-throughput sequencing (ATAC-seq). We identify a large number of layer-specific accessible sites, and significant association with genes that are expressed in specific cortical layers. Integration of these data with layer-specific transcriptomic profiles and transcription factor binding motifs enabled us to construct a regulatory network revealing potential key layer-specific regulators, including <i>Cux1/2</i>, <i>Foxp2</i>, <i>Nfia</i>, <i>Pou3f2</i>, and <i>Rorb</i>. This dataset is a valuable resource for identifying candidate layer-specific cis-regulatory elements in adult mouse cortex.