Transcriptional induction of DLC-1 gene through Sp1 sites by histone deacetylase inhibitors in gastric cancer cells.
We previously reported that trichostatin A (TSA), a histone deacetylase (HDAC) inhibitor, induced DLC-1 mRNA expression and accumulated acetylated histones H3 and H4 associated with the DLC-1 promoter in DLC-1 non-expressing gastric cancer cells. In this study, we demonstrated the molecular mechanisms by which TSA induced the DLC-1 gene expression. Treatment of the gastric cancer cells with TSA activates the DLC-1 promoter activity through Sp1 sites located at -219 and -174 relative to the transcription start site. Electrophoretic mobility-shift assay (EMSA) revealed that Sp1 and Sp3 specifically interact with these Sp1 sites and showed that TSA did not change their binding activities. The ectopic expression of Sp1, but not Sp3, enhances the DLC-1 promoter responsiveness by TSA. Furthermore, the TSA-induced DLC-1 promoter activity was increased by p300 expression and reduced by knockdown of p300. These results demonstrated the requirement of specific Sp1 sites and dependence of Sp1 and p300 for TSA-mediated activation of DLC-1 promoter.
Kim
Tai Young
TY
National Research Laboratory for Cancer Epigenetics, Cancer Research Institute, Seoul National University College of MedicineSeoul 110-744, Korea.
Kim
In Sook
IS
Jong
Hyun Soon
HS
Lee
Jung Weon
JW
Kim
Tae You
TY
Jung
Mira
M
Bang
Yung Jue
YJ
D045744:Cell Line, Tumor; D024202:Electrophoretic Mobility Shift Assay; D020690:GTPase-Activating Proteins; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D011401:Promoter Regions, Genetic; D016329:Sp1 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D051705:Sp3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D013274:Stomach Neoplasms / Q000378:metabolism*; D014158:Transcription, Genetic; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis* / Q000235:genetics; D050880:p300-CBP Transcription Factors / Q000235:genetics / Q000378:metabolism
C112352:DLC1 protein, human; D020690:GTPase-Activating Proteins; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; C497121:SP3 protein, human; D016329:Sp1 Transcription Factor; D025521:Tumor Suppressor Proteins; D051705:Sp3 Transcription Factor; C012589:trichostatin A; D050880:p300-CBP Transcription Factors; D006655:Histone Deacetylases