Histone deacetylase inhibitor apicidin induces cyclin E expression through Sp1 sites.
We show that a histone deacetylase (HDAC) inhibitor apicidin increases the transcriptional activity of cyclin E gene, which results in accumulation of cyclin E mRNA and protein in a time- and dose-dependent manner. Interestingly, apicidin induction of cyclin E gene is found to be mediated by Sp1- rather than E2F-binding sites in the cyclin E promoter, as evidenced by the fact that specific inhibition of Sp1 leads to a decrease in apicidin activation of cyclin E promoter activity and protein expression, but mutation of E2F-binding sites of cyclin E promoter region fails to inhibit the ability of apicidin to activate cyclin E transcription. In addition, this transcriptional activation of cyclin E by apicidin is associated with histone hyperacetylation of cyclin E promoter region containing Sp1-binding sites. Our results demonstrate that regulation of histone modification by an HDAC inhibitor apicidin contributes to induction of cyclin E expression and this effect is Sp1-dependent.
Kim
Soyoung
S
College of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
Kang
Jae Ku
JK
Kim
Yong Kee
YK
Seo
Dong-Wan
DW
Ahn
Seong Hoon
SH
Lee
Jae Cheol
JC
Lee
Chang-Hee
CH
You
Jueng-Soo
JS
Cho
Eun-Jung
EJ
Lee
Hyang Woo
HW
Han
Jeung-Whan
JW
D001665:Binding Sites; D019927:Cyclin E / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects*; D006367:HeLa Cells; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000378:metabolism*; D006801:Humans; D010456:Peptides, Cyclic / Q000008:administration & dosage*; D008926:Plicamycin / Q000008:administration & dosage*; D011485:Protein Binding; D015398:Signal Transduction / Q000187:drug effects*; D016329:Sp1 Transcription Factor / Q000378:metabolism*; D015533:Transcriptional Activation / Q000187:drug effects
D019927:Cyclin E; D056572:Histone Deacetylase Inhibitors; D010456:Peptides, Cyclic; D016329:Sp1 Transcription Factor; C102351:apicidin; D006655:Histone Deacetylases; D008926:Plicamycin