Blood: In acute lymphoblastic leukemia, E2A-PBX1 is the secondary activation factor of RUNX1

E2A is a basic helix-ring-helix (bHLH) transcription factor that plays a vital role in determining the fate of tissue-specific cells, including B-cell spectral differentiationIn 5% of children with acute lymphoblastic leukemia (ALL), the t (1,19) chromosome translocation specifically targets the E2A gene, producing a cancer-causing E2A-PBX1 fusion proteinAlthough previous studies have shown that E2A-PBX1 is carcinogenic in both cellular and animal models, the E2A-PBX1-reinforced cistrome, E2A-PBX1 interactions, and the mechanisms associated with the occurrence of leukemia are still unclearIn this study, the researchers identified the direct target site of E2A-PBX1 in t (1,19) positive pre-B ALL, and showed that E2A-PBX1 prioritized a subset of gene sites (p300, MED1, and H3K27 acetylyl) combined with RUNX1 and gene activation mechanisms compared to normal E2Athrough biochemical analysis, the researchers further discovered that E2A-PBX1 interacts directly with RUNX1 through a region that spans the PBX1 homologous domainThe results also show that the binding of E2A-PBX1 to gene enhancers depends on interaction with RUNX1, not on DNA binding activity in the E2A-PBX1 homologous domaintranscriptome analysis and cell transformation analysis further established the target gene activation and important RUNX1 requirements for E2A-PBX1-mediated gene activation and leukemiaIt is worth noting that the RUNX1 bit itself is also directly activated by E2A-PBX1, indicating that there is a multi-layered interaction between E2A-PBX1 and RUNX1, this study is the first to conduct an unbiased spectrum analysis of E2A-PBX1cistrome in pre-B ALL cells, revealing a previously undiscovered path: E2A-PBX1 works with RUNX1 to promote transcription changes in pre-B ALL