Embryonic expression and regulation of the large zinc finger protein KRC.

Abstract

KRC fusion proteins bind to the kappaB enhancer motif and to the signal sequences of V(D)J recombination. Here we have characterized endogenous KRC in mouse embryos and lymphoma cell lines. Starting from midgestation, neuronal- and lymphoid-restricted expression of KRC was observed from the dorsal root ganglia, trigeminal ganglion, thymus, and cerebral cortex. Several B-cell lines produced an alternatively spliced KRC transcript of 4.5 kb and a 115-kDa DNA-binding protein isoform. Additionally, that KRC transcript was induced by lipopolysaccharide, a potent activator of cells in immunity and inflammation. In genetic-engineered B cells stably transfected with inducible expression vectors for the recombination activating genes RAG1, RAG2, or both, the avidity of KRC to DNA was markedly decreased when RAG1 and RAG2 were overexpressed. We hypothesize that KRC may function in developing thymocytes and neurons, where its role might be transcription regulation or DNA recombination.