Loss of SATB1 alters 3D genome architecture in aged mouse T cells
Declining levels of the chromatin organizer SATB1 disrupt genomic boundaries and drive inflammatory gene activation in naive CD4+ T cells.
Science advances · Wang B et al. · Paper published 2 Oct 2026
In mice, aging alters the three-dimensional genome organization and transcriptional programs of naive CD4+ T cells. Researchers found that aged naive CD4+ T cells exhibit weakened topologically associating domain boundaries, rewired enhancer-promoter interactions, and increased expression of inflammatory and activation-related genes. Mechanistically, these structural changes stem partly from the age-associated decline of the chromatin organizer SATB1. In young T cells, SATB1 colocalizes with CTCF to spatially constrain CTCF-binding sites. As SATB1 levels fall with age, the spatial range of CTCF-mediated interactions expands without changing CTCF occupancy. Furthermore, conditionally deleting SATB1 in naive T cells reproduced both the 3D genome disruption and the transcriptional shifts observed in naturally aged cells.
Why it matters
These findings show that deteriorating 3D chromatin architecture drives immune cell dysfunction, linking the loss of structural genome organizers to age-related inflammation.
Caveats
The study was conducted exclusively in mice, so whether identical SATB1-mediated architectural changes govern naive T cell aging in humans requires direct confirmation.
Written from the paper’s abstract, and every claim checked against it before publishing. Read the paper for the full methods and data.
The paper
Aging-associated SATB1 deficiency remodels 3D genome architecture and transcriptional programs in naive CD4⁺ T cells
Wang B, Ji L, Bian Q
Science advances · 2 Oct 2026 · Peer-reviewed
- Relevance
- Core geroscience
- News value
- Important
- Evidence
- Animals
- Status
- Peer-reviewed
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