Title: "The balance between Tcf-1 and beta catenin is critical to secure genome stability in thymocytes"
Speaker: Dr. Fotini Gounari, Knapp Center for Lupus and Immunology Research, University of Chicago
The T-cell specific HMG domain factor Tcf-1 depends on its interaction with β-catenin to promote gene transcription. We show here that Tcf-1, one of the most abundantly expressed genes in double positive (DP) thymocytes, binds actively transcribing loci despite limiting amounts of β-catenin. Tcf-1, and RAG2 overlap at common histone-3-tri-methylated at lysine-4 chromatin sites genome-wide. In addition, Tcf-1 binds the DNA-repair protein Ku70 and elevated b-catenin levels outcompete this interaction resulting in altered resolution of RAG induced DNA-double-strand-breaks and increased DNA-damage. At the same time, elevated b-catenin levels enable survival of cells with damaged DNA. This combination culminates in RAG-dependent lymphomas with recurring Tcra/Myc oncogenic translocations. Our findings reveal a novel Tcf-1 function in DNA-repair that is controlled by b-catenin and
suggest how it can be compromised in carcinogenesis.