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Proto-oncogene FBI-1 (Pokemon/ZBTB7A) represses transcription of the tumor suppressor Rb gene via binding competition with Sp1 and recruitment of co-repressors.

FBI-1 (also called Pokemon/ZBTB7A) is a BTB/POZ-domain Kr├╝ppel-like zinc-finger transcription factor. Recently, FBI-1 was characterized as a proto-oncogenic protein, which represses tumor suppressor ARF gene transcription. The expression of FBI-1 is increased in many cancer tissues. We found that FBI-1 potently represses transcription of the Rb gene, a tumor suppressor gene important in cell cycle arrest. FBI-1 binds to four GC-rich promoter elements (FREs) located at bp -308 to -188 of the Rb promoter region. The Rb promoter also contains two Sp1 binding sites: GC-box 1 (bp -65 to -56) and GC-box 2 (bp -18 to -9), the latter of which is also bound by FBI-1. We found that FRE3 (bp -244 to -236) is also a Sp1 binding element. FBI-1 represses transcription of the Rb gene not only by binding to the FREs, but also by competing with Sp1 at the GC-box 2 and the FRE3. By binding to the FREs and/or the GC-box, FBI-1 represses transcription of the Rb gene through its POZ-domain, which recruits a co-repressor-histone deacetylase complex and deacetylates histones H3 and H4 at the Rb gene promoter. FBI-1 inhibits C2C12 myoblast cell differentiation by repressing Rb gene expression.

Pubmed ID: 18801742

Authors

  • Jeon BN
  • Yoo JY
  • Choi WI
  • Lee CE
  • Yoon HG
  • Hur MW

Journal

The Journal of biological chemistry

Publication Data

November 28, 2008

Associated Grants

None

Mesh Terms

  • ADP-Ribosylation Factors
  • Animals
  • Cell Cycle
  • Cell Differentiation
  • DNA-Binding Proteins
  • Drosophila melanogaster
  • HeLa Cells
  • Histone Deacetylases
  • Histones
  • Humans
  • Myoblasts
  • Protein Binding
  • Protein Structure, Tertiary
  • Proto-Oncogene Proteins
  • Response Elements
  • Retinoblastoma Protein
  • Sp1 Transcription Factor
  • Transcription Factors
  • Transcription, Genetic