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

Tahir H. Tahirov, Ko Sato, Emi Ichikawa-Iwata, Motoko Sasaki, Taiko Inoue-Bungo, Masaaki Shiina, Kazumi Kimura, Shioka Takata, Atsushi Fujikawa, Hisayuki Morii, Takashi Kumasaka, Masaki Yamamoto, Shunsuke Ishii, Kazuhiro Ogata

Research output: Contribution to journalArticle

127 Scopus citations

Abstract

c-Myb, but not avian myeloblastosis virus (AMV) v-Myb, cooperates with C/EBPβ 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/EBPβ DBD, and a promoter DNA fragment. Within the c-Myb complex, a DNA-bound C/EBPβ 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/EBPβ observed in crystal mimics their long range interaction on the promoter, which is accompanied by intervening DNA looping.

Original languageEnglish (US)
Pages (from-to)57-70
Number of pages14
JournalCell
Volume108
Issue number1
DOIs
StatePublished - Jan 11 2002

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Tahirov, T. H., 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. (2002). Mechanism of c-Myb-C/EBPβ cooperation from separated sites on a promoter. Cell, 108(1), 57-70. https://doi.org/10.1016/S0092-8674(01)00636-5