Characterization of the DNA binding of Ikaros protein using three dimensional modeling and rapid prototyping technology

Human hematopoiesis is controlled by the coordinated activity of various genes. The Ikaros gene encodes a DNA‐binding protein that is essential for normal hematopoiesis and acts as a tumor suppressor. The absence of Ikaros leads to the severe impairment of lymphocyte development. Deletion of the Ikaros gene, or the loss of Ikaros activity, has been associated with human B and T cell acute lymphoblastic leukemia (ALL). Ikaros binds DNA in a sequence‐specific manner with four C2H2 zinc finger motifs that are located at the N‐terminal end of the protein. DNA binding is an essential part of Ikaros’ function – to regulate expression of the genes that are involved in cellular differentiation and proliferation. Ikaros binds to the upstream regulatory elements of its target genes and regulates their transcription via chromatin remodeling. The Edgewood Campus School SMART (Students Modeling a Research) Team has built an accurate three‐dimensional model of the zinc finger motifs of the Ikaros protein binding to DNA using 3D printing technology. By modeling the Ikaros‐DNA interaction, we hope to provide new insights into the mechanism of Ikaros’ function, as well as to the specificity of its protein‐DNA recognition. This information will help in understanding the role of Ikaros in normal hematopoiesis and in preventing the development of leukemia. Supported by grants from HHMI Pre‐College Program and NIH‐NCRR‐SEPA.