Histone deacetylase 3 represses p15(INK4b) and p21(WAF1/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 p15(INK4b) and p21(WAF1/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 p15(INK4b) and p21(WAF1/cip1) transcription by interacting with Sp1. Furthermore, knockdown of HDAC3 by RNAi up-regulated the transcriptional expression of p15(INK4b), but not that of p21(WAF1/cip1), implicating the different roles of HDAC3 in repression of p15(INK4b) and p21(WAF1/cip1) transcription. Data from this study indicate that the inhibition of p15(INK4b) and p21(WAF1/cip1) may be one of the mechanisms by which HDAC3 participates in cell cycle regulation and oncogenesis.
Huang
Weifeng
W
Institute of Genetics and Cytology, Northeast Normal University, Changchun 130024, China.
Tan
Dapeng
D
Wang
Xiuli
X
Han
Songyan
S
Tan
Jiang
J
Zhao
Yanmei
Y
Lu
Jun
J
Huang
Baiqu
B
D002460:Cell Line; D050762:Cyclin-Dependent Kinase Inhibitor p15 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D017930:Genes, Reporter; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D034741:RNA, Small Interfering / Q000235:genetics; D016329:Sp1 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D000099186:Histone Deacetylase 3
D050762:Cyclin-Dependent Kinase Inhibitor p15; D006655:Histone Deacetylases; D034741:RNA, Small Interfering; D016329:Sp1 Transcription Factor; D000099186:Histone Deacetylase 3