PINAUD, E. | Search bioRxiv

bioRxiv2026

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

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.

immunology↗

bioRxiv2023

Core enhancers of the 3'RR optimize IgH nuclear position and loop conformation for oriented CSR

Class switch recombination is an essential process which enabling B cells to adapt immunoglobulin subtypes to antigens. Transcription plays a crucial role in regulating CSR in which the IgH 3Regulatory Region (3RR) was identified as a key player. The 3RR stands at the 3 end of IgH locus and is composed of four core enhancers surrounded by inverted repeated sequences, forming a quasi-palindrome. In addition to transcriptional control, nuclear organization appears to be an important level in CSR regulation. Furthermore, the chromatin loops at IgH locus facilitate an efficient CSR recombination by bringing the donor and acceptor switch regions closer together. However, the precise control mechanisms governing both of these processes remain partially understood. Here, using the reference DNA 3D-FISH technique combined with various high throughput approaches, we showed that 3RR core enhancers are necessary and sufficient to preorganize resting B cell nuclei to facilitate a deletional CSR mechanism at activated stage. We demonstrated that the 3RR core enhancers regulate IgH locus addressing in the nuclei, control IgH locus accessibility and orchestrate IgH loops formation. Our findings pinpointed an additional regulation level of mechanisms underlying B cell diversification. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=184 SRC="FIGDIR/small/548507v1_ufig1.gif" ALT="Figure 1"> View larger version (41K): org.highwire.dtl.DTLVardef@69ca5aorg.highwire.dtl.DTLVardef@1640c29org.highwire.dtl.DTLVardef@15a7949org.highwire.dtl.DTLVardef@d0af7e_HPS_FORMAT_FIGEXP M_FIG C_FIG Position of IgH loci through B cell development (from transitional to stimulated stages) is represented by the red spots. In wt and c3RR context, IgH loci get closer from each other and from nucleus center during evolution from transitional to mature resting stage and they relocates more at nuclear periphery, away one from each other, upon in vitro stimulation. In{Delta} 3RR model, this dynamic is lost and, moreover, IgH loci are more localized to pericentromeric heterochromatin (represented by green area) since the mature resting B cell stage and remain in after in vitro stimulation.

immunology↗