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

被引:131
作者
Tahirov, TH
Sato, K
Ichikawa-Iwata, E
Sasaki, M
Inoue-Bungo, T
Shiina, M
Kimura, K
Takata, S
Fujikawa, A
Morii, H
Kumasaka, T
Yamamoto, M
Ishii, S
Ogata, K
机构
[1] Kanagawa Acad Sci & Technol, Kanazawa Ku, Yokohama, Kanagawa 2360004, Japan
[2] Yokohama City Univ, Sch Med, Dept Biol Struct, Kanazawa Ku, Yokohama, Kanagawa 2360004, Japan
[3] Yokohama City Univ, Sch Med, Dept Biochem, Kanazawa Ku, Yokohama, Kanagawa 2360004, Japan
[4] Yokohama City Univ, Sch Med, Dept Pathol, Kanazawa Ku, Yokohama, Kanagawa 2360004, Japan
[5] Yokohama City Univ, Sch Med, Dept Urol, Kanazawa Ku, Yokohama, Kanagawa 2360004, Japan
[6] RIKEN, Tsukuba Inst, Mol Genet Lab, Tsukuba, Ibaraki 3050074, Japan
[7] Japan Sci & Technol Corp, CREST Res Project, Tsukuba, Ibaraki 3050074, Japan
[8] Natl Inst Adv Ind Sci & Technol, Prot Dynam Grp, Cent 6, Tsukuba, Ibaraki 3058566, Japan
[9] RIKEN, Harima Inst, SPring 8, Biocrystallog Technol Div, Sayo, Hyogo 6795148, Japan
[10] RIKEN, Harima Inst, SPring 8, Struct Biophys Lab, Sayo, Hyogo 6795148, Japan
关键词
D O I
10.1016/S0092-8674(01)00636-5
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
c-Myb, but not avian myeloblastosis virus (AMV) v-Myb, cooperates with C/EBPbeta 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/EBPbeta DBD, and a promoter DNA fragment. Within the c-Myb complex, a DNA-bound C/EBPbeta 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/EBPbeta observed in crystal mimics their long range interaction on the promoter, which is accompanied by intervening DNA looping.
引用
收藏
页码:57 / 70
页数:14
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