Regulation of T-cell receptor Dβ1 promoter by KLF5 through reiterated GC-rich motifs

摘要: Rearrangement of T-cell receptor (TCR) and immunoglobulin genes by a common V(D)J recombination machinery is regulated developmentally specific chromatin changes at the target locus, process associated with transcription. At TCRβ Eβ enhancer Dβ1 promoter regulate germline transcription originating near TCR gene segment. The contains 3 GC-rich motifs that bind set nuclear proteins from pro–T-cell lines. Mutations diminish binding also activity in transcriptional reporter assays. Using yeast one-hybrid approach, Kruppel-like factors—KLF3, KLF5, KLF6—and novel zinc finger protein were identified thymus library, all which bound motif sequence-specific manner. Of these genes, KLF5 mRNA was expressed restricted manner lymphoid cells tissues, highest expression lines Rag-deficient thymocytes. Antibody supershift studies immunoprecipitation assay confirmed promoter. In assays, but not KLF6 efficiently transactivated promoter, whereas dominant-negative construct inhibited expression. These data suggest reiterated GC contribute to through other Kruppel family members may lineage-specific regulation