TAD cliques predict key features of chromatin organization

Abstract

Background Mechanisms 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. Results We find that TAD long-range interactions are connected to many key features of chromatin organization, including open and closed compartments, compaction and loop extrusion processes. 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 process. Conclusions Our results shed light on the organizational principles that govern repressive and active domains in the human genome.

Loss of multi-level 3D genome organization during breast cancer progression

“…3C). This trend aligns with our previous subcompartment characterization of TAD cliques and reaffirms that TAD cliques are distinct from subcompartments (Liyakat Ali et al 2021). Comparing subcompartment associations across the three stages, reveals that cliques of size >5 are generally B2-enriched in T1 and C1, and thus the subcompartment composition of larger cliques is altered in these two stages relative to 10A (Supplementary Fig.…”

Emerging Roles of Repetitive and Repeat-Containing RNA in Nuclear and Chromatin Organization and Gene Expression

“…Traditionally, Cohesin, loop extrusion, and CCCTC-binding factor (CTCF) have been proposed to create TADs to regulate gene expression. TADs boundaries are enriched for the insulator binding protein CTCF, housekeeping genes, transfer RNAs, and short interspersed element (SINE) retrotransposons, indicating that these factors may have a role in establishing the topological domain structure of the genome ( Liyakat Ali et al, 2021 ). Cohesin can utilize its ATPase activity to extrude loops of chromatin and this is limited by CTCF-occupied insulator DNA elements ( Sanborn et al, 2015 ; Fudenberg et al, 2017 ).…”

Stage-specific dynamic reorganization of genome topology shapes transcriptional neighborhoods in developing human retinal organoids

“…Long-range inter-TAD agglomerations (i.e., TAD cliques) are proposed to be associated with many key features of chromatin organization 68 and play an important role in development. 12 , 69 To further explore the relationship between TADs and retinal development, we called TAD cliques as previously described 12 (see STAR Methods , Figure 4E ).…”