Expression and splicing of Ikaros family members in murine and human thymocytes

Abstract

Abstract The Ikaros family of transcription factors consists of five highly homologous zinc-finger proteins: Ikaros, Helios, Eos, Aiolos and Pegasus. These family members can homodimerize or heterodimerize in any combination which can alter transcriptional activity. Ikaros family member function can further vary with alternative splicing that affects DNA-binding. Previous studies have demonstrated that abolishing the function of the entire Ikaros family blocks lymphocyte development. Whereas eliminating the function of one Ikaros family member results in relatively minor defects. These data indicate that multiple Ikaros family members play a role in lymphocyte development. The goal of this study was to fully characterize expression and splicing of Ikaros family members in murine and human T cell development from the CD4−CD8− double negative (DN) developmental stage to the CD4+CD8+ double positive (DP) stage. In both mice and humans, Aiolos and Ikaros mRNA levels increase during the progression of T cell development from the DN to DP stages. However, the corresponding increase in Aiolos and Ikaros protein levels was only observed in mice. Additionally, extensive alternative splicing of Ikaros and Aiolos was observed in mice, but only Ikaros was extensively spliced in humans. Helios mRNA and protein levels decreased during murine T cell development, but increased in human T cell development. These data indicate that differences in human and murine T cell development may be regulated by differences in Ikaros family member expression and splicing.