title: Mechanism of c-Myb-C/EBP beta cooperation from separated sites on a promoter.
abstract: c-Myb, but not avian myeloblastosis virus (AMV) v-Myb, cooperates with C/EBP beta to regulate transcription of myeloid-specific genes. To assess the structural basis for that difference, we determined the crystal structures of complexes comprised of the c-Myb or AMV v-Myb DNA-binding domain (DBD), the C/EBP beta DBD, and a promoter DNA fragment. Within the c-Myb complex, a DNA-bound C/EBP beta interacts with R2 of c-Myb bound to a different DNA fragment; point mutations in v-Myb R2 eliminate such interaction within the v-Myb complex. GST pull-down assays, luciferase trans-activation assays, and atomic force microscopy confirmed that the interaction of c-Myb and C/EBP beta observed in crystal mimics their long range interaction on the promoter, which is accompanied by intervening DNA looping.
authors.affiliation: Kanagawa Academy of Science and Technology, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan. tahir@med.yokohama-cu.ac.jp
authors.forename: Tahir H
authors.initials: TH
authors.lastname: Tahirov
authors.forename: Ko
authors.initials: K
authors.lastname: Sato
authors.forename: Emi
authors.initials: E
authors.lastname: Ichikawa-Iwata
authors.forename: Motoko
authors.initials: M
authors.lastname: Sasaki
authors.forename: Taiko
authors.initials: T
authors.lastname: Inoue-Bungo
authors.forename: Masaaki
authors.initials: M
authors.lastname: Shiina
authors.forename: Kazumi
authors.initials: K
authors.lastname: Kimura
authors.forename: Shioka
authors.initials: S
authors.lastname: Takata
authors.forename: Atsushi
authors.initials: A
authors.lastname: Fujikawa
authors.forename: Hisayuki
authors.initials: H
authors.lastname: Morii
authors.forename: Takashi
authors.initials: T
authors.lastname: Kumasaka
authors.forename: Masaki
authors.initials: M
authors.lastname: Yamamoto
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Ishii
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Ogata
mesh_terms: D000123:Acetyltransferases; D000595:Amino Acid Sequence; D001665:Binding Sites / Q000235:genetics; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D003461:Crystallography; D006801:Humans; D008969:Molecular Sequence Data; D016296:Mutagenesis / Q000502:physiology; D009690:Nucleic Acid Conformation; D020626:Oncogene Proteins v-myb / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000502:physiology*; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000235:genetics; D016271:Proto-Oncogene Proteins c-myc / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D013329:Structure-Activity Relationship; D015533:Transcriptional Activation / Q000502:physiology
chemical_list: D022782:CCAAT-Enhancer-Binding Protein-beta; D020626:Oncogene Proteins v-myb; D011506:Proteins; D016271:Proto-Oncogene Proteins c-myc; D000123:Acetyltransferases; C077509:mim-1 protein, Gallus gallus