Model for RUNX1 regulation of PU.1 interaction with corepressors. Proposed model for RUNX1-mediated regulation of the transcriptional activity of PU.1 in normal hematopoiesis, and effects of RUNX1 deletions and translocations on this cooperation. RUNX1 and PU.1 independently interact with SIN3A or ETO2 (rows 1 and 2). When both RUNX1 and PU.1 are present, ETO2 and SIN3A are excluded from the RUNX1:PU.1 complex (row 3). Corepressor exclusion requires the RUNX1 C-terminus. Therefore, RUNT does not inhibit PU.1 interaction with corepressor (row 4). Similarly, corepressor is recruited to the RUNX1-ETO/PU.1 complex (RUNX1-ETO lacks the C-terminus). In this complex, corepressor is recruited to both the ETO moiety of the leukemia fusion protein and to PU.1 (row 5).