Multi-level remodelling of chromatin underlying activation of human T cells
Details
Publication Year 2021-01-12, Volume 11, Issue #1, Page 528
Journal Title
Scientific Reports
Abstract
Remodelling of chromatin architecture is known to regulate gene expression and has been well characterized in cell lineage development but less so in response to cell perturbation. Activation of T cells, which triggers extensive changes in transcriptional programs, serves as an instructive model to elucidate how changes in chromatin architecture orchestrate gene expression in response to cell perturbation. To characterize coordinate changes at different levels of chromatin architecture, we analyzed chromatin accessibility, chromosome conformation and gene expression in activated human T cells. T cell activation was characterized by widespread changes in chromatin accessibility and interactions that were shared between activated CD4(+) and CD8(+) T cells, and with the formation of active regulatory regions associated with transcription factors relevant to T cell biology. Chromatin interactions that increased and decreased were coupled, respectively, with up- and down-regulation of corresponding target genes. Furthermore, activation was associated with disruption of long-range chromatin interactions and with partitioning of topologically associating domains (TADs) and remodelling of their TAD boundaries. Newly formed/strengthened TAD boundaries were associated with higher nucleosome occupancy and lower accessibility, linking changes in lower and higher order chromatin architecture. T cell activation exemplifies coordinate multi-level remodelling of chromatin underlying gene transcription.
WEHI Research Division(s)
Population Health And Immunity; Immunology; Bioinformatics
PubMed ID
33436846
Open Access at Publisher's Site
https://doi.org/10.1038/s41598-020-80165-9
NHMRC Grants
NHMRC/1037321
Rights Notice
Refer to copyright notice on published article.


Creation Date: 2021-03-09 08:05:45
Last Modified: 2021-03-09 08:35:04
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