Mechanism of c-Myb–C/EBPβ Cooperation from Separated Sites on a Promoter

1 Kanagawa Academy of Science and tion assays, and atomic force microscopy confirmed that the interaction of c-Myb and C/EBP␤ observed in Technology (KAST) 3-9 Fukuura crystal mimics their long range interaction on the promoter , which is accompanied by intervening DNA Kanazawa-ku Yokohama 236-0004 looping. Japan Japan the DNA into sufficiently close proximity to enable them 8 Protein Dynamics Group to form nucleoprotein complexes (Schleif, 1992). Thus National Institute of Advanced Industrial Science far, however, there is very little structural evidence on and Technology an atomic scale that explains the synergistic trans-acti-Central 6 vation by distantly separated transcription factors. For 1-1-1 Higashi example, it was modeled that an oligomerization domain Tsukuba separated from a DNA-binding domain acts as an in-Ibaraki 305-8566 ducer of DNA looping in the case of lac repressor-pro-Japan moter DNA interaction (Friedman et al., 1995). Here, we 9 Bio-Crystallography Technology Division address this problem in the case of the synergistic trans-10 Structural Biophysics Laboratory activation of myeloid genes by c-Myb and C/EBP␤. RIKEN Harima Institute / SPring-8 The c-myb proto-oncogene product (c-Myb) is an es-1-1-1 Kouto sential regulator of proliferation and differentiation of Mikazuki hematopoietic cells (Lipsick and Wang, 1999). c-Myb Sayo acts as a transcriptional regulatory factor (Weston and Japan modulating expression of various target genes in the hematopoietic system, in many cases with cooperation of a wide variety of other transcriptional regulatory factors , including members of the CAAT-enhancer binding cooperates with C/EBP␤ to regulate transcription of frequently observed and well-characterized c-Myb part-myeloid-specific genes. To assess the structural basis ners, regulating transcription of such hematopoietic for that difference, we determined the crystal struc