4.8 Article

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

期刊

ADVANCED SCIENCE
卷 9, 期 30, 页码 -

出版社

WILEY
DOI: 10.1002/advs.202202149

关键词

3D genome; DNA density; nuclear lamina; single-cell Hi-C

资金

  1. National Science Foundation of China [32125009, 32070663, 62172325, 32070134]
  2. Fundamental Research Funds for the Central Universities
  3. Natural Science Basic Research Program of Shaanxi [2021GXLH-Z-098]
  4. Science and Technology Project of Xi'an [21RGSF0013]
  5. Key Construction Program of the National 985 Project

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This study introduces two global physical properties, DNA density and distance to nuclear periphery, and constructs a 2D matrix called D-2 plot for mapping genetic and epigenetic markers. Functional markers on the D-2 plot show distinct patterns, indicating its ability to compartmentalize functional genome regions. Furthermore, this study successfully identifies constantly active and newly activated genes during olfactory sensory neuron maturation based on the trajectories on the D-2 plot. The research reveals that the D-2 plot effectively categorizes functional regions and provides a universal and transcription-related measurement for the 3D genome.
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, D-2 plot, is constructed for mapping genetic and epigenetic markers. Distinct patterns of functional markers on the D-2 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 D-2 plot, the constantly active and newly activated genes are successfully identified during olfactory sensory neuron maturation. The analysis reveals that the D-2 plot effectively categorizes functional regions and provides a universal and transcription-related measurement for the 3D genome.

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