Toward an understanding of the relation between gene regulation and 3D genome organization

Abstract The development and usage of chromosome conformation capture technologies have provided great details on 3D genome organization and provide great opportunities to understand how gene regulation is affected by the 3D chromatin structure. Previously, we identified two types of sequence domains, CGI forest and CGI prairie, which tend to segregate spatially, but to different extent in different tissues/cell states. To further quantify the association of domain segregation with gene regulation and differentiation, we analyzed in this study the distribution of genes of different tissue specificities along the linear genome, and found that the distribution patterns are distinctly different in forests and prairies. The tissue-specific genes (TSGs) are significantly enriched in the latter but not in the former and genes of similar expression profiles among different cell types (co-activation/repression) also tend to cluster in specific prairies. We then analyzed the correlation between gene expression and the spatial contact revealed in Hi-C measurement. Tissue-specific forest-prairie contact formation was found to correlate with the regulation of the TSGs, in particular those in the prairie domains, pointing to the important role gene positioning, in the linear DNA sequence as well as in 3D chromatin structure, plays in gene regulatory network formation.