Human encodes several histone H3-Lysine 4 (H3K4) specific methyl-transferases (HMTs) such as MLL1 (mixed lineage leukemia 1), MLL2, MLL3, hSet1 etc, that play critical roles in gene expression. These HMTs are present as distinct multi-protein complexes with several proteins in common. Herein, we have affinity purified and characterized human CpG binding protein (CGBP) and its interacting proteins from human cells. We demonstrated that CGBP is co-purified with three H3K4 specific HMTs MLL1, MLL2, and hSet1. We also performed independent immuno-precipitation of MLL1, MLL2 and hSet1 complexes from human cell and demonstrated that each of these complexes contains CGBP. In addition, CGBP is co-localized with MLL1, MLL2 and hSet1 in vivo and binds to the promoter of MLL target gene HoxA7. Antisense mediated knock down of CGBP diminished the recruitment of MLL1 and down regulated levels of H3K4 trimethylation in HoxA7 promoter affecting its expression. These results demonstrated that CGBP interacts with MLL1, MLL2 as well as hSet1 HMTs and plays critical roles in regulations of MLL target genes.