Genome-wide studies identify a novel interplay between AML1 and AML1/ETO in t(8;21) acute myeloid leukemia

摘要: The AML1/ETO fusion protein is essential to the development of t(8;21) acute myeloid leukemia (AML) and well recognized for its dominant-negative effect on coexisting wild-type AML1. However, genome-wide interplay between AML1 remains elusive in leukemogenesis AML. Through chromatin immunoprecipitation sequencing computational analysis, followed by a series experimental validations, we report here that able orchestrate expression targets regardless being activated or repressed; this achieved via forming complex with recruiting cofactor AP-1 chromatin. On occupancy, largely overlap preferentially bind adjacent distinct short long motifs colocalized regions, respectively. physical interaction, can form chromatin, runt homology domain both proteins are responsible their interactions. More importantly, relative binding signals determine which genes repressed AML1/ETO. Further analysis coregulators indicates transactivates gene through AML1/ETO-AML1 complex. These findings enrich our knowledge understanding significance oncogenic leukemia.