Mechanism of c-Myb-C/EBP beta cooperation from separated sites on a promoter

Cell. 2002 Jan 11;108(1):57-70. doi: 10.1016/s0092-8674(01)00636-5.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetyltransferases*
  • Amino Acid Sequence
  • Binding Sites / genetics
  • CCAAT-Enhancer-Binding Protein-beta / chemistry
  • CCAAT-Enhancer-Binding Protein-beta / genetics*
  • CCAAT-Enhancer-Binding Protein-beta / metabolism*
  • Crystallography
  • Humans
  • Molecular Sequence Data
  • Mutagenesis / physiology
  • Nucleic Acid Conformation
  • Oncogene Proteins v-myb / chemistry
  • Oncogene Proteins v-myb / genetics
  • Oncogene Proteins v-myb / metabolism
  • Promoter Regions, Genetic / physiology*
  • Protein Structure, Tertiary
  • Proteins / genetics
  • Proto-Oncogene Proteins c-myc / chemistry
  • Proto-Oncogene Proteins c-myc / genetics*
  • Proto-Oncogene Proteins c-myc / metabolism*
  • Structure-Activity Relationship
  • Transcriptional Activation / physiology


  • CCAAT-Enhancer-Binding Protein-beta
  • Oncogene Proteins v-myb
  • Proteins
  • Proto-Oncogene Proteins c-myc
  • Acetyltransferases
  • mim-1 protein, Gallus gallus

Associated data

  • PDB/1H88
  • PDB/1H89
  • PDB/1H8A