title: Oct-1 is involved in the transcriptional repression of the p15(INK4b) gene.
abstract: 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.
authors.affiliation: Department of Molecular-Targeting Cancer Prevention, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Hitomi
authors.forename: Youichirou
authors.initials: Y
authors.lastname: Matsuzaki
authors.forename: Shusuke
authors.initials: S
authors.lastname: Yasuda
authors.forename: Mayumi
authors.initials: M
authors.lastname: Kawanaka
authors.forename: Shingo
authors.initials: S
authors.lastname: Yogosawa
authors.forename: Makoto
authors.initials: M
authors.lastname: Koyama
authors.forename: Dean
authors.initials: D
authors.lastname: Tantin
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Sakai
mesh_terms: D002460:Cell Line; D016922:Cellular Senescence / Q000235:genetics; D050762:Cyclin-Dependent Kinase Inhibitor p15 / Q000235:genetics*; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D050811:Octamer Transcription Factor-1 / Q000502:physiology*; D012097:Repressor Proteins / Q000502:physiology*; D014158:Transcription, Genetic; D014162:Transfection
chemical_list: C493966:CDKN2B protein, human; D050762:Cyclin-Dependent Kinase Inhibitor p15; D050811:Octamer Transcription Factor-1; D012097:Repressor Proteins