Structural analyses of DNA recognition by the AML1/Runx-1 Runt domain and its allosteric control by CBF beta

The core binding factor (CBF) heterodimeric transcription factors comprised of AML/CBFA/PEBPSalpha/Runx and CBF beta /PEBP2 beta subunits are essentia l for differentiation of hematopoietic and bone cells, and their mutation i s intimately related to the development of acute leukemias and cleidocrania l dysplasia. Here, we present the crystal structures of the AML1/Runx-1/CBF alpha (Runt domain)-CBF beta (core domain)-C/EBP beta (b-Zip)-DNA, AML1/Ru nx-1/CBF alpha (Runt domain)-C/EBP beta (bZip)-DNA, and AML1/Runx-1/CBF alp ha (Runt domain)DNA complexes. The hydrogen bonding network formed among CB F alpha (Runt domain) and CBF beta, and CBF alpha (Runt domain) and DNA rev ealed the allosteric regulation mechanism of CBF alpha (Runt domain)-DNA bi nding by CBF beta. The point mutations of CBF alpha related to the aforemen tioned diseases were also mapped and their effect on DNA binding is discuss ed.