Revealing Gene Function and Transcription Relationship by Reconstructing Gene-Level Chromatin Interaction

Area of Science:

• Genomics
• Molecular Biology
• Epigenetics

Background:

• Chromatin organization in human nuclei is hierarchical and influences gene transcription and cell fate.
• The concept of transcription factories suggests spatial interactions among genes within the nucleus.
• Direct visualization of gene spatial interactions, function, and co-transcription remains a challenge.

Purpose of the Study:

• To investigate whether function-related genes co-locate in 3D space for co-transcription.
• To develop a framework for studying the relationship between gene function, co-transcription, and spatial interaction.
• To explore the impact of 3D genome organization on gene transcription.

Main Methods:

• Construction of matrices using gene ontology annotations, high-throughput chromosome conformation capture (Hi-C) data, and RNA-seq data.
• Comparative analysis of gene pairs across twenty human tissues and cell lines.
• Analysis of spatial reorganization effects on gene clusters, such as histone gene clusters.

Main Results:

• 3D genome organization predominantly influences gene transcription at the local scale.
• Local genes within family clusters exhibit similar transcription patterns.
• Spatial reorganization of a histone gene cluster was found to control gene transcription.

Conclusions:

• Function-related genes tend to be spatially proximate and are coordinately activated or repressed.
• The study provides a genome-wide framework for analyzing the interplay between gene function, co-transcription, and spatial organization.
• Local genome architecture plays a significant role in regulating gene expression patterns.