In summary, these studies demonstrate that TIP60 negatively modulates c-Myb transcriptional activity by recruiting histone deacetylases in human hematopoietic cells, leading us to hypothesize that TIP60 is a normal regulator of c-Myb function and that dysregulated or mutated TIP60 may contribute to c-Myb-driven leukemogenesis.
Here, we show that chromobox homolog 8 (CBX8), a Polycomb Group protein that interacts with MLL-AF9 and TIP60, is required for MLL-AF9-induced transcriptional activation and leukemogenesis.
Using E(mu)-myc transgenic mice that are heterozygous for a Tip60 gene (Htatip) knockout allele (hereafter denoted as Tip60+/- mice), we show that Tip60 counteracts Myc-induced lymphomagenesis in a haplo-insufficient manner and in a time window that is restricted to a pre- or early-tumoral stage.
Importantly, these results suggest that p30II functions as a novel retroviral modulator of Myc-TIP60-transforming interactions that may contribute to adult T-cell leukemogenesis.