Multi-level remodelling of chromatin underlying activation of human T cells
Files
(Published version)
Date
2021
Authors
Bediaga, N.G.
Coughlan, H.D.
Johanson, T.M.
Garnham, A.L.
Naselli, G.
Schröder, J.
Fearnley, L.G.
Bandala-Sanchez, E.
Allan, R.S.
Smyth, G.K.
Editors
Advisors
Journal Title
Journal ISSN
Volume Title
Type:
Journal article
Citation
Scientific Reports, 2021; 11(1):528-1-528-16
Statement of Responsibility
Naiara G. Bediaga, Hannah D. Coughlan, Timothy M. Johanson, Alexandra L. Garnham, Gaetano Naselli, Jan Schröder, Liam G. Fearnley, Esther Bandala, Sanchez, Rhys S. Allan, Gordon K. Smyth and Leonard C. Harrison
Conference Name
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 longrange 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.
School/Discipline
Dissertation Note
Provenance
Description
Access Status
Rights
© 2021, The Author(s). This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.