Overall, these data suggest that formation of IKAROS-EZH2 complex is essential for H3K27me3 enrichment and formation of facultative heterochromatin the first day after Ikzf1 re-expression, and that EZH2 DNA binding in Ikzf1-null T-ALL is not associated with H3K27me3 enrichment. Here, EZH2 is linked to acute lymphoblastic leukemia.