Fingerprinting Ikaros

The DNA binding transcription factor protein Ikaros contains four so-called "zinc finger" domains that are shown to work together in different combinations to regulate distinct genes in mice, including genes required for leukemia suppression, reports a study published online in Nature Immunology.

Many transcription factors possess so-called zinc finger domains that bind DNA and thereby control gene expression. Though it is known that Ikaros regulates immune cell development, how its individual zinc finger domains contribute to the control of gene expression is not entirely understood. Previous studies have shown that fingers 2 and 3 are required to bind DNA and flanking fingers 1 and 4 contribute to sequence recognition. Moreover, in humans, mutations in IKZF1, the gene encoding Ikaros, are associated with multiple types of leukemia.

To understand the functions of zinc finger 1 and 4, Steve Smale and colleagues generated mice lacking these individual domains of Ikaros. Finger-specific loss led to different defects in immune cell generation and importantly mice lacking finger 4 develop thymic lymphomas, revealing a tumor suppressor role for Ikaros finger 4.