Histone deacetylase 3 represses p15INK4b and p21WAF1/cip1 transcription by interacting with Sp1

Histone deacetylase 3 (HDAC3) has been implicated to play roles in governing cell proliferation. Here we demonstrated that the overexpression of HDAC3 repressed transcription of p15INK4b and p21WAF1/cip1 genes in 293T cells, and that the recruitment of HDAC3 to the promoter regions of these genes was critical to this repression. We also showed that HDAC3 repressed GAL4-Sp1 transcriptional activity, and that Sp1 was co-immunoprecipitated with FLAG-tagged HDAC3. We conclude that HDAC3 can repress p15INK4b and p21WAF1/cip1 transcription by interacting with Sp1. Furthermore, knockdown of HDAC3 by RNAi up-regulated the transcriptional expression of p15INK4b, but not that of p21WAF1/cip1, implicating the different roles of HDAC3 in repression of p15INK4b and p21WAF1/cip1 transcription. Data from this study indicate that the inhibition of p15INK4b and p21WAF1/cip1 may be one of the mechanisms by which HDAC3 participates in cell cycle regulation and oncogenesis.