2026/05/01 by Gabriel Dolsten, Ze Wang, Xiao Jun Huang +13 · 1 voice
Immunology and Microbiology · Biochemistry, Genetics and Molecular Biology · #T-cell and B-cell Immunology #Genomics and Chromatin Dynamics #Immune Cell Function and Interaction
paper · pdf · doi:10.1016/j.celrep.2026.117341
Recent studies have advanced understanding of chromosomal organization and its role in gene regulation, yet most analyses focus on short-range interactions (<2 Mb), limiting insight into broader architecture. The relationships between topologically associating domains (TADs), sub-TAD loops, cross-TAD interactions, and chromosomal compartmentalization remain poorly understood. Here, using high-resolution Hi-C analysis, we identify extensive multi-megabase and interchromosomal interactions (metaloops) in T lymphocytes that organize into meta-TAD associations (metadomains). These metaloops connect distal promoters and regulatory elements of genes functionally important in T cells, including Ctla4 , Ikzf2 , Il2ra , Ets1 , and Foxo1 . Reanalysis of mouse and human datasets confirms their reproducibility and dependence on superenhancers. Genome-wide clustering reveals three distinct interchromosomal hubs, including a superenhancer-enriched hub linked to T cell-specific gene activation. Integrative analysis of regulatory genomics data identifies factors associated with short- versus long-range interactions. This study introduces a broadly applicable computational framework and reveals features of T cell genome organization.