Project description:TCF-1 is an HMG family transcription factor which is known to be activated by the canonical Wnt signaling pathway and modulated by other signals such as those derived from T cell receptor. We found that during CD8 T cell responses, TCF-1 deficiency impaired long-term maintenance of antigen-specific memory CD8 T cells. We used microarrays to detect gene expression changes in memory CD8 T cells caused by TCF-1 deficiency. Host mice that received WT or TCF-1-deficient OT-I CD8 T cells were infected with attenuated Listeria monocytogenes expressing Ova peptide. In memory phase (i.e., more than 80 days post infection), antigen-specific T cells were ioslated by cell sorting. RNA was extracted and hybridized to GeneChip Mouse GENE 1.0 ST arrays (Affymetrix).
Project description:Cellular binary fate decisions require the progeny to silence genes associated with the alternative fate. The major subsets of alpha:beta T cells have been extensively studied as a model system for fate decisions. While the transcription factor RUNX3 is required for the initiation of Cd4 silencing in CD8 T cell progenitors, it is not required to maintain the silencing of Cd4 and other helper T lineage genes. The other runt domain containing protein, RUNX1, silences Cd4 in an earlier T cell progenitor, but this silencing is reversed whereas the gene silencing after RUNX3 expression is not reverse. Therefore, we hypothesized that RUNX3 and not RUNX1 recruits other factors that maintains the silencing of helper T lineage genes in CD8 T cells. To this end, we performed a proteomics screen of RUNX1 and RUNX3 to determine candidate silencing factors.
Project description:TCF-1 is an HMG family transcription factor which is known to be activated by the canonical Wnt signaling pathway and modulated by other signals such as those derived from T cell receptor. We found that during CD8 T cell responses, TCF-1 deficiency impaired long-term maintenance of antigen-specific memory CD8 T cells. We used microarrays to detect gene expression changes in memory CD8 T cells caused by TCF-1 deficiency.