Metadomain genome associations in mammalian T cells (CD4/CD8 data)

For example, the relationships between different topologically associating domains (TADs) and sub-TAD regulatory loops are uncertain due to the lack of appropriate computational tools and high-resolution experimental data. Herein, we developed a computational methodology for studying chromosomal organization across scales and applied it to high-resolution chromosome conformation capture (Hi-C) data using activatory and inhibitory lineages of T lymphocytes as a model.

We identified shared and cell type-specific TADs and sub-TAD loops at 5 Kb resolution. Global analysis revealed megabase-scale and inter-chromosomal interactions, including many cell type-specific meta-TAD associations (meta-domains) containing multiple functionally important genes such as Ctla4, Ikzf2, Ets1, Lef1, Runx1, Bach2, Foxo1 and others. Reanalysis of published data confirmed the reproducibility of these metadomain interactions in both mouse and human T cells.