D² Plot, a Matrix of DNA Density and Distance to Periphery, Reveals Functional Genome Regions

The execution of biological activities inside space-limited cell nuclei requires sophisticated organization. Current studies on the 3D genome focus on chromatin interactions and local structures, e.g., topologically associating domains (TADs). In this study, two global physical properties: DNA density and distance to nuclear periphery (DisTP), are introduced and a 2D matrix, D² plot, is constructed for mapping genetic and epigenetic markers. Distinct patterns of functional markers on the D² plot, indicating its ability to compartmentalize functional genome regions, are observed. Furthermore, enrichments of transcription-related markers are concatenated into a cross-species transcriptional activation model, where the nucleus is divided into four areas: active, intermediate, repress and histone, and repress and repeat. Based on the trajectories of the genomic regions on D² plot, the constantly active and newly activated genes are successfully identified during olfactory sensory neuron maturation. The analysis reveals that the D² plot effectively categorizes functional regions and provides a universal and transcription-related measurement for the 3D genome.