Figure 2. Neuronal Activity-Induced DNA DSBs Form at Early-Response Genes.

(A) Genomic regions were categorized into 14 distinct chromatin states based on combinatorial patterns of various chromatin marks (Figure S2A). The percentage of γH2AX peaks within each chromatin state were then normalized to the proportion of the genome with that chromatin state and plotted.

(B) γH2AX ChIP-seq signals enriched in NMDA-treated samples relative to controls were processed using CEAS (Cis-Regulatory Element Annotation System) program (http://liulab.dfci.harvard.edu/CEAS/). (Left) Pie chart depicting the relative proportions of the indicated annotated regions in the genome. (Right) Disposition of γH2AX signals within these annotated genomic regions.

(C) Differential peak calling was performed to determine the regions that were enriched for γH2AX following NMDA treatment (Experimental Procedures). This data were then processed using CIRCOS software (Krzywinski et al., 2009) to generate the shown circular representation. The outer ring depicts the mouse chromosomes. The blue ring represents a map of gene densities, and the green ring indicates γH2AX signals. Red lines within the green ring represent loci that were enriched for γH2AX relative to controls. Twenty loci were within genes, and these genes are indicated. One locus was within intergenic regions.

(D) UCSC genome browser views depicting the disposition of γH2AX signals within various activity-regulated genes under basal conditions (control) and following NMDA treatment, y axis represents intensity and the range is indicated in parentheses.