Epigenomic tomography for probing spatially-defined chromatin state in the brain

Here we demonstrate brain epigenomic tomography that is constructed via epigenomic profiling of mouse neocortex slices with sub-millimeter thickness using a low-input ChIP-seq technology. We profiled the variation in histone modification signal (H3K27me3 and H3K27ac) across these slices and grouped the spatial epigenomic features into clusters of various spatial variation patterns. Overall design: We processed mouse neocortex into 0.5 mm thick coronal slices and separated them into left and right hemisphere pieces. We extracted nuclei from each tissue piece and sorted them into neuron and glia using FACS. Nuclei were digested with MNase for MOWChIP-seq of H3K27me3 and H3K27ac. RNA-seq libraries were generated using Smart-seq2. The filename contains information on the mouse from which the tissue for the experiment was isolated from (M1-M5), the hemisphere of the brain the tissue belonged to (left/right), the number of slice of the tissue (01-22, from anterior to posterior), the type of nuclei sorted for the experiment (neuron/glia), the target being profiled (H3K27me3, H3K27ac, RNA), and replicate number. 2 technical replicates were conducted for each sample. For example, "M1-Left-01-Glia-H3K27me3-R1" refers to technical replicate 1 of the ChIP-seq assay of H3K27me3 using glia nuclei isolated from slice 1 of left hemisphere of mouse 1.