Multi-Level Chromosome Remodeling Underlying Activation of Human T Cells

Chromatin remodeling is fundamental in regulating gene transcription. Cell lineage-specific chromatin remodeling is well described but less is known about remodeling in response to cell perturbation. Therefore, because immune cells exhibit major changes in gene expression upon activation we characterized chromatin accessibility, 3D genome interactions and gene expression in activated primary human CD4+ and CD8+ T cells, and mature B cells. Chromatin structure was cell type-specific and regions of altered chromatin accessibility upon T-cell activation were enriched for regulatory elements and enhancer RNAs, genetic variants linked to immune disorders, transcription factor binding sites relevant to T-cell function and to differential expression of specific genes. At a higher level of chromosome structure, T-cell activation was followed by acquisition of new topologically-associating domain (TAD) boundaries and partitioning into smaller TADs linked to gene transcription at specific loci. These findings connect features of chromosome remodeling to gene expression in activated human T cells.