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

Abstract

Chromatin is hierarchically organized in human interphase nuclei. Dynamic chromatin interactions are thought to influence gene transcription and cell fate determination. A consensus concept is that genes may form transcription factories within nucleus by spatially interaction. However, it is still not well known whether the function-related genes co-locate in three-dimensional (3D) space for co-transcription. Especially, there is a lack of visualization method that directly reflect the relationship between gene spatial interaction, gene function and co-transcription. In this study, we constructed three kinds of matrices based on gene ontology annotations, high-through chromosome conformation capture (Hi-C) data and RNA-seq data from twenty human tissues and cell lines. The comparative analysis for gene pairs revealed that 3D genome organization influences gene transcription predominantly at local scale. We found that the local genes within family clusters have similar transcription patterns. We also found that spatial reorganization of a histone gene cluster could control gene transcription. These observations suggest that function-related genes are close in space and activated or repressed together. Our work provided a framework for genome-wide studying the relationship between gene function, co-transcription and spatial interaction.