Abstract
Ikaros proteins are essential for the development or differentiation of fetal hematopoietic stem cells into lymphoid lineages. It is expressed during embryogenesis only in sites of hematopoiesis, and in the adult in early B cells, Tcell progenitors, and mature Tcells. All Ikaros isoforms share a common C-terminal domain but vary in the number of N-terminal zincfinger domains. At least three N-terminal zinc fingers are required for an Ikaros protein to bind DNA specifically and with high affinity. The C-terminal domain is essential for dimerization and high-affinity DNA binding. Ikaros proteins with fewer than three N-terminal zinc fingers can act in a dominant-negative fashion, interfering with the DNA binding of other Ikaros isoforms. High-affinity binding sites for Ikaros have been identified in the regulatory regions of many lymphocyte-specific genes.
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