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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Acetyltransferases*
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Amino Acid Sequence
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Binding Sites / genetics
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CCAAT-Enhancer-Binding Protein-beta / chemistry
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CCAAT-Enhancer-Binding Protein-beta / genetics*
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CCAAT-Enhancer-Binding Protein-beta / metabolism*
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Crystallography
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Humans
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Molecular Sequence Data
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Mutagenesis / physiology
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Nucleic Acid Conformation
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Oncogene Proteins v-myb / chemistry
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Oncogene Proteins v-myb / genetics
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Oncogene Proteins v-myb / metabolism
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Promoter Regions, Genetic / physiology*
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Protein Structure, Tertiary
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Proteins / genetics
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Proto-Oncogene Proteins c-myc / chemistry
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Proto-Oncogene Proteins c-myc / genetics*
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Proto-Oncogene Proteins c-myc / metabolism*
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Structure-Activity Relationship
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Transcriptional Activation / physiology
Substances
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CCAAT-Enhancer-Binding Protein-beta
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Oncogene Proteins v-myb
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Proteins
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Proto-Oncogene Proteins c-myc
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Acetyltransferases
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mim-1 protein, Gallus gallus
Associated data
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PDB/1H88
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PDB/1H89
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PDB/1H8A