Oct-1 is involved in the transcriptional repression of the p15(INK4b) gene

p15(INK4b) functions as a tumor suppressor and implicated in cellular senescence. Here, we show that the Oct-1 binding site in the human p15(INK4b) gene promoter functions as a silencer. Oct-1 specifically interacts with this binding site in vitro and in vivo and SMRT and HDAC1 are present in the p1...

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Bibliographic Details
Published in:FEBS letters 2007-03, Vol.581 (6), p.1087-1092
Main Authors: Hitomi, Toshiaki, Matsuzaki, Youichirou, Yasuda, Shusuke, Kawanaka, Mayumi, Yogosawa, Shingo, Koyama, Makoto, Tantin, Dean, Sakai, Toshiyuki
Format: Article
Language:English
Subjects:
Cell Line
Cellular Senescence - genetics
Cyclin-Dependent Kinase Inhibitor p15 - genetics
Gene Expression Regulation - physiology
Humans
Octamer Transcription Factor-1 - physiology
Repressor Proteins - physiology
Transcription, Genetic
Transfection
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Summary:p15(INK4b) functions as a tumor suppressor and implicated in cellular senescence. Here, we show that the Oct-1 binding site in the human p15(INK4b) gene promoter functions as a silencer. Oct-1 specifically interacts with this binding site in vitro and in vivo and SMRT and HDAC1 are present in the p15(INK4b) proximal promoter region. Moreover, mouse embryo fibroblasts (MEFs) lacking Oct-1 have shown significantly increased levels of p15(INK4b) protein compared to their normal counterparts. Treatment with a histone deacetylase (HDAC) inhibitor has activated the expression of p15(INK4b) in wild-type MEFs but has no effect in MEFs lacking Oct-1, suggesting that Oct-1 represses p15(INK4b) gene expression in an HDAC-dependent manner. Finally, we show that the expression of Oct-1 protein significantly decreases, whereas p15(INK4b) protein significantly increases with the cellular aging process. Taken together, these results suggest that Oct-1 is an important transcriptional repressor for p15(INK4b) gene and the transcriptional repression of the p15(INK4b) gene by Oct-1 may be one of the regulatory mechanisms of cellular senescence.
ISSN:0014-5793
DOI:10.1016/j.febslet.2007.01.092