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Analysis of 3-dimensional genome of exhausted CD8+ T cells reveals a critical role of IRF8 in their terminal differentiation in cancer [RNA]

GSE277972 Mus musculus Expression profiling by high throughput sequencing 4 samples Submitted 2025/09/30 Platform GPL21273
Summary
Exhausted CD8+ T cell differentiation is accompanied by extensive changes in epigenome. However, whether and how higher-order chromatin organization is involved in exhausted CD8+ T cell differentiation is unclear. Here, we showed extensive changes in the three-dimensional genome during exhausted CD8+ T cell differentiation, associated with changes in gene transcription. Moreover, we identified Interferon regulatory factor 8 (IRF8) as an essential transcription factor in re-organization of spatial chromosomal interactions. Irf8 deficiency inhibits the development of terminal exhausted CD8+ T cells and promotes tumor growth. Mechanistically, IRF8 bound to genes associated with exhausted CD8+ T cells differentiation and promoted the formation of chromosomal loops. At the loop anchor regions, IRF8 recruited CTCF to form active chromosomal structure to regulated exhaustion-associated genes. These results thus identify a critical role of IRF8-dependent chromatin topology in gene transcription during exhausted CD8+ T cell differentiation.
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Also filed as BioProject PRJNA1165137 and SRA study SRP534649. Searching any of these in the dataset finder brings you back here.

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