Inhibition of CBF/NF-Y mediated transcription activation arrests cells at G2/M phase and suppresses expression of genes activated at G2/M phase of the cell cycle

Previous studies showed that binding of the CBF/NF-Y (CBF) transcription factor to cellular promoters is essential for cell proliferation. This observation prompted us to investigate the function of CBF in relation to cell cycle progression and in cell-cycle-regulated transcription. In this study, w...

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Published in:Nucleic acids research 2006-12, Vol.34 (21), p.6272-6285
Main Authors: Hu, Qianghua, Lu, Jing-Fang, Luo, Rong, Sen, Subrata, Maity, Sankar N
Format: Article
Language:English
Subjects:
Adenoviridae - genetics
Aurora Kinases
CCAAT-Binding Factor - antagonists & inhibitors
CCAAT-Binding Factor - genetics
CCAAT-Binding Factor - metabolism
Cell Division - genetics
Cyclin B - genetics
Cyclin B1
G2 Phase - genetics
Genetic Vectors
HeLa Cells
Humans
Molecular Biology
Promoter Regions, Genetic
Protein Structure, Tertiary
Protein-Serine-Threonine Kinases - genetics
Sequence Deletion
TATA-Box Binding Protein - metabolism
Tetracycline - pharmacology
Transcriptional Activation
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Summary:Previous studies showed that binding of the CBF/NF-Y (CBF) transcription factor to cellular promoters is essential for cell proliferation. This observation prompted us to investigate the function of CBF in relation to cell cycle progression and in cell-cycle-regulated transcription. In this study, we used a tetracycline-inducible adenoviral vector to express a truncated CBF-B subunit, Bdbd, lacking a transcription activation domain in various mammalian cell lines. The Bdbd polypeptide interacts with cellular CBF-A/CBF-C and binds to promoters containing CBF-binding sites. Interestingly, expression of Bdbd in various mammalian cells resulted in the inhibition of cell proliferation and specific cell cycle arrest at G2/M phase. Gene expression analysis demonstrated that the expression of Bdbd strongly suppressed cell cycle-dependent transcription activation of Cyclin B1, Aurora A and CDK1 genes, key regulators for cell cycle progression at G2/M phase. Chromatin immunoprecipitation analysis showed that Bdbd significantly inhibited binding of TATA-binding protein, TBP to both Cyclin B1 and Aurora A promoters, but did not inhibit binding of E2F3 activator to Cyclin B1 promoter. This study suggested that the activation domain of CBF-B plays an essential role in the transcription activation of Cyclin B1 and Aurora A genes at G2/M phase, thus regulating cell cycle progression at G2/M phase.
ISSN:0305-1048
1362-4962
DOI:10.1093/nar/gkl801