Results identified novel IKAROS and HDAC1 functions in T-ALL: Both IKAROS and HDAC1 are essential for EZH2 histone methyltransferase activity and formation of facultative heterochromatin; recruitment of HDAC1 by IKAROS is critical for establishment of H3K27me3 histone modification and repression of active enhancers; and IKAROS-HDAC1 complexes promote formation and expansion of H3K27me3 Large Organized Chromatin lysine (K) domains (LOCKs) and Broad Genic Repression Domains (BGRDs) in T-ALL. Here, IKZF1 is linked to acute lymphoblastic leukemia.