Structure of Ikaros. The N-terminal portion of Ikaros contains a DNA-binding domain with 4 zinc finger motifs. There are 2 zinc finger motifs at the C-terminal end that are essential for the formation of Ikaros homodimers. Ikaros binds directly to DNA to positively (green) or negatively (red) regulate expression of target genes. Internal deletions in exons 4 to 7 are common alterations that attenuate the DNA-binding capacity of Ikaros, and these deletions produce a dominant-negative isoform that results in loss of tumor-suppressor function of the WT allele, so that the transcriptional activity is lost (exons not drawn to actual scale).⁷