TAD cliques predict key features of chromatin organization

Abstract

Processes underlying genome 3D organization and domain formation in the mammalian nucleus are not completely understood. Multiple processes such as transcriptional compartmentalization, DNA loop extrusion and interactions with the nuclear lamina dynamically act on chromatin at multiple levels. Here, we explore long-range interaction patterns between topologically associated domains (TADs) in several cell types. We find that this is connected to many key features of chromatin organization, including open and closed compartments, compaction and loop extrusion processes. We find that domains that form large TAD cliques tend to be repressive across cell types, when comparing gene expression, LINE/SINE repeat content and chromatin subcompartments. Further, TADs in large cliques are larger in genomic size, less dense and depleted of convergent CTCF motifs, in contrast to smaller and denser TADs formed by a loop extrusion processes. Our results shed light on the organizational principles that govern repressive and active domains in the human genome.