Histone deacetylase 3 represses p15(INK4b) and p21(WAF1/cip1) transcription by interacting with Sp1

Biochem Biophys Res Commun. 2006 Jan 6;339(1):165-71. doi: 10.1016/j.bbrc.2005.11.010. Epub 2005 Nov 10.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Cyclin-Dependent Kinase Inhibitor p15 / antagonists & inhibitors
  • Cyclin-Dependent Kinase Inhibitor p15 / genetics
  • Cyclin-Dependent Kinase Inhibitor p15 / metabolism*
  • Genes, Reporter
  • Histone Deacetylases / genetics
  • Histone Deacetylases / metabolism*
  • Humans
  • Promoter Regions, Genetic
  • Protein Binding
  • RNA, Small Interfering / genetics
  • Sp1 Transcription Factor / genetics
  • Sp1 Transcription Factor / metabolism*
  • Transcription, Genetic*

Substances

  • Cyclin-Dependent Kinase Inhibitor p15
  • RNA, Small Interfering
  • Sp1 Transcription Factor
  • Histone Deacetylases
  • histone deacetylase 3