Y. Sowa et al., Sp3, but not Sp1, mediates the transcriptional activation of the p21/WAF1/Cip1 gene promoter by histone deacetylase inhibitor, CANCER RES, 59(17), 1999, pp. 4266-4270
We previously reported that both sodium butyrate and trichostatin A (TSA),
both of which are known as inhibitors of histone deacetylase, arrest human
tumor cells at G(1) and G(2)-M and activate the cyclin-dependent kinase inh
ibitor, the p21/WAF1/Cip1 gene promoter, through the Spl sites. In this stu
dy, we identified Sp1 and Sp3 as major factors binding to the Spl sites of
the p21/WAF1/Cip1 promoter in MG63 cells through electrophoretic mobility s
hift assays and showed that TSA treatment did not change their binding acti
vities. However, GAL4-Sp3 but not GAL4-Sp1 fusion protein supported the TSA
-mediated gene induction from a luciferase reporter plasmid driven by five
GAL4 DNA-binding sites. Moreover, the ectopic expression of dominant negati
ve Sp3 repressed the enhancement by TSA of the p21/WAF1/Cip1 promoter and S
pl site-driven promoter. Taken together, these results suggest that histone
deacetylase inhibitor up-regulates p21/WAF1/Cip1 transcription by Sp3 but
not by Sp1.