SATB1 is required for CD8 coreceptor reversal.
Intrathymic signals induce the differentiation of immature CD4(+)CD8(+) double positive (DP) thymocytes into mature CD4(+) or CD8(+) single positive (SP) T cells. The transcriptional mechanism by which CD8 lineage is determined is not fully understood. The best evidence, which favors the kinetic signaling/coreceptor reversal model, indicates that signaled DP thymocytes terminate CD8 transcription prior to their subsequent re-initiation of CD8 transcription and ultimate differentiation into CD8SP T cells. We and others have shown that CD8 lineage commitment is severely perturbed in mice in which expression of the transcription factor SATB1 is either conventionally knocked out or T cell-specifically knocked down. Here, we demonstrate that, as with normal thymocytes, cultured SATB1-deficient DP thymocytes inactivate CD8 coreceptor transcription following receipt of signals (PMA plus ionomycin) that mimic TCR-mediated positive selection. However, this terminated CD8 transcription is not re-initiated by signals (IL-7) conducive to CD8 differentiation in SATB1-deficient DP. We show that SATB1 specifically binds to a cis-regulatory element within the CD8 enhancer (E8(III)) known to be required for coreceptor reversal. A requirement in CD8 coreceptor reversal identifies SATB1 as an essential trans-regulator of CD8 lineage fate, whose action may be mediated via recruitment to the E8(III) DP enhancer.
Nie
Hui
H
Section of Molecular Genetics and Microbiology and Institute for Cellular and Molecular Biology, University of Texas at Austin, 1 University Station A5000, Austin, TX 78712-0162, United States.
Yao
Xin
X
Maika
Shanna D
SD
Tucker
Philip W
PW
D000818:Animals; D001665:Binding Sites; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D004742:Enhancer Elements, Genetic / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D015851:Interleukin-7 / Q000494:pharmacology; D036961:Matrix Attachment Region Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D051379:Mice; D011485:Protein Binding / Q000187:drug effects; D011956:Receptors, Cell Surface / Q000276:immunology*
D015851:Interleukin-7; D036961:Matrix Attachment Region Binding Proteins; D011956:Receptors, Cell Surface; C469541:Satb1 protein, mouse