Transcriptional Repression Of P15～(INK4B) And P21～(WAF1/cip1) Genes By HDAC3

Histone deacetylase 3 (HDAC3) has been implicated to play roles in governing cellproliferation. Here, we demonstrated that the overexpression of HDAC3 repressedtranscription of p15^INK4B and p21^WAF1/cip1 genes in 293T cells, and that the recruitment ofHDAC3 to the promoter regions of these genes was critical to this repression. We alsoshowed that HDAC3 repressed GAL4-Sp1 transcriptional activity, and that Sp1 wasco-immunoprecipitated with FLAG-tagged HDAC3. We conclude that HDAC3 can repressp15^INK4B and p21^WAF1/cip1 transcription by interacting with Sp1. Furthermore, knockdown ofHDAC3 by RNAi up-regulated the transcriptional expression of p15^INK4B, but not that ofp21^WAF1/cip1, implicating the different roles of HDAC3 in repression of p15^INK4B andp21^WAF1/cip1 transcription. Data from this study indicate that the inhibition of p15^INK4B andp21^WAF1/cip1 may be one of the mechanisms by which HDAC3 participates in cell cycleregulation and oncogenesis.