Extended Data Fig. 8: SATB1 binds to genomic regions that show differential accessibility during exhausted T cell differentiation.

(a-c) Naïve CD45.2⁺ SATB1-deficient P14 cells (Satb1^flex/flex/Cd8^Cre, SATB1-KO) or control cells (Satb1^flex/flex) P14 cells were adoptively transferred into naïve wildtype CD45.1⁺ mice which were subsequently infected with LCMV-Docile. On 21 p.i., CD62L⁺ and CD62L⁻ T_PEX and CX3CR1⁺ and CD101⁺ T_EX cells were sorted from either SATB1-KO or control spleens and used for RNA and ATAC-sequencing. Shown are SATB1 ChIP binding and gene accessibility in indicated cell types. (a) Ifng, (b) Slamf1, Slamf6, and (c) Arid5a, Ccr5 and Prdm1. (d-i) Mixed bone marrow chimeric mice containing SATB1-DNA-binding mutant (Satb1^m1Anu/m1Anu) (CD45.2⁺) and control T cells (CD45.1/2⁺) were infected with LCMV-Docile. On day 21 p.i. spleens were analyzed using flow cytometry. (d) Flow cytometry plots and quantification showing frequencies of activated Gp33⁺ Satb1^m1Anu/m1Anu or control cells. (e) Flow cytometry plots and quantification showing frequencies of Satb1^m1Anu/m1Anu or control T_PEX and T_EX cells. (f) Expression of TCF1 and Ly108 in Gp33⁺ Satb1^m1Anu/m1Anu or control T_PEX cells. (g) Flow cytometry plots and quantification showing frequencies of Satb1^m1Anu/m1Anu or control CD62L⁺ T_PEX cells. (h) Flow cytometry plots and quantification showing frequencies of Satb1^m1Anu/m1Anu or control CX3CR1⁺ and CD101⁺ T_EX cells. (i) Flow cytometry plots and quantification showing frequencies of IFN-γ and TNF producing Satb1^m1Anu/m1Anu or control cells after stimulation with Gp33 peptide ex vivo. Flow cytometry plots are representative. Dots in graphs represent individual mice; horizontal lines and error bars of bar graphs indicate means ± SEM, respectively. Data are pooled from two independent experiments. P values are from two-tailed unpaired student’s t test.