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bioRxiv · 10.64898/2026.07.22.739998

Lineage-specific regulation and RNA-associated functions of SATB1 in mature B-cells

Frayssinhes, J.-Y. A.·Meriot, L.·Marchiol, T.·Pinault, E.·Forne, T.·Spilianakis, C.·PINAUD, E.·Le Noir, S.
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Abstract

Special AT-rich binding protein 1 (SATB1) is a nuclear matrix-associated transcription factor that orchestrates higher-order chromatin architecture and gene expression in T and B lymphocytes. While SATB1s role in T cells is well-established, its regulation and function in B cells remain underexplored. Here, we showed that Satb1 expression in mature B cells is controlled by alternative promoter usage and splicing, with promoters P1 and P3 dynamically switching upon LPS-induced activation, while P2 remains transcriptionally silent. We identified four Satb1 mRNA isoforms, including two novel transcripts ({Delta}9 and{Delta} 9{Delta}11), all of which maintain open reading frames. Satb1 transcription decreases upon activation while SATB1 protein content evolves differently, suggesting post-transcriptional regulation. SATB1 forms a high-molecular-weight complex in B cells, and co-immunoprecipitation mass spectrometry reveals RNA-binding proteins as its predominant interactors. These findings specify SATB1 expression kinetics during B-cell activation and reveal its role as a regulator of RNA splicing in B cells.

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Frayssinhes, J.-Y. A., Meriot, L., Marchiol, T., Pinault, E., Forne, T., Spilianakis, C., PINAUD, E., Le Noir, S.. 2026-07-24. Lineage-specific regulation and RNA-associated functions of SATB1 in mature B-cells. https://doi.org/10.64898/2026.07.22.739998

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