p300 collaborates with Sp1 and Sp3 in p21(waf1/cip1) promoter activation induced by histone deacetylase inhibitor

We have reported that histone acetylation induced by trichostatin A (TSA) p romotes p21(waf1/cip1) (p21) expression, the GC-box located just upstream o f TATA box was responsible for TSA-induced promoter activation, and both Sp l and Sp3 were the working activator of this GC-box, To understand the mole cular pathway from histone acetylation to this Spl family factors-mediated promoter activation, we investigated the function of p300, one of the histo ne acetyltransferase, in the present work. The evidence supporting the link age between p300 and TSA-induced p21 promoter activation were realized from the following findings: 1) cotransfection of p300 elevated pal promoter ac tivity, and this elevation was dependent on TSA-responsive GC-box; 2) TSA-i nduced promoter activation was blocked by the introduction of p300 dominant -negative mutant into cells; and 3) Sp1- or Sp3-mediated activation was als o suppressed by this p300 dominant-negative mutant. Our data also suggested that p300 collaborates with Spl in a way which is different from that when p300 collaborates with p53 in p21 transcription.