Oct-1 is involved in the transcriptional repression of the p15INK4b gene

p15INK4b functions as a tumor suppressor and implicated in cellular senescence. Here, we show that the Oct-1 binding site in the human p15INK4b 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 p15INK4b proximal promoter region. Moreover, mouse embryo fibroblasts (MEFs) lacking Oct-1 have shown significantly increased levels of p15INK4b protein compared to their normal counterparts. Treatment with a histone deacetylase (HDAC) inhibitor has activated the expression of p15INK4b in wild-type MEFs but has no effect in MEFs lacking Oct-1, suggesting that Oct-1 represses p15INK4b gene expression in an HDAC-dependent manner. Finally, we show that the expression of Oct-1 protein significantly decreases, whereas p15INK4b protein significantly increases with the cellular aging process. Taken together, these results suggest that Oct-1 is an important transcriptional repressor for p15INK4b gene and the transcriptional repression of the p15INK4b gene by Oct-1 may be one of the regulatory mechanisms of cellular senescence.