Fig. 4.

Schematic representation of IKZF1 isoforms and the proposed model for dominant-negative isoforms participating in CRLF2 overexpression. Overview of the human family of IKAROS Family Zinc Finger 1 (IKZF1) gene and its isoforms (IK1 to IK10). IKZF1 isoforms that retain at least three DNA binding zinc fingers (ZF, represented by the pink bar), maintain their functional effect and are called “long isoforms” (IK1 to IK3). On the other hand, the isoforms that lose two or more of these ZFs, are unable to bind DNA, but they retain their capability to form heterodimers with IKZF1 long isoforms leading to a dominant-negative effect. Physiologically, IKZF1 directly binds to the CRLF2 promoter and suppresses its expression through enrichment of H3K9me3 (represented by the red cross in the figure) [9,10,26].