Immunoprecipitation and mass spectrometry (IP-MS) on KAT6A chimeras

Despite KAT6A chimeras potent oncogenic activity, the mechanisms by which KAT6A fusion proteins achieve genomic specificity and drive leukemogenesis remain poorly understood. Previous studies suggest that the leukemogenic potential of KAT6A-TIF2 depends on its chromatin-binding ability rather than its histone acetyltransferase (HAT) activity, with oncogenicity further amplified by CBP recruitment through its fusion partners. The winged helix domain (WH1) of KAT6A can bind unmethylated CpG islands and interact with P300/CBP via the TAZ2 domain. However, the widespread presence of unmethylated CpG islands across the genome does not fully explain the genomic specificity of KAT6A-CBP (K/C) and KAT6A-P300 (K/P) fusions, leaving key mechanistic gaps unexplored. To uncover protein interactions underlying these genomic associations, we performed immunoprecipitation and mass spectrometry (IP-MS) on KAT6A N-terminus and chimeras. Mass spectrometry analysis was performed to identify the core components of the KAT6A complex and the interacting proteins of KAT6A.