*3.2. p300 Histone Acetyltransferase (HAT) Domain Expression and Purification*

Enzymatically-active p300 HAT was prepared as previously described [44]. Briefly, p300 HAT and Sir2 expression plasmids (generous gifts from Phillip Cole) were co-transformed into *E. coli* BL21 AI cells (Invitrogen, Carlsbad, CA, USA). Cells were grown at 37 ◦C in Terrific Broth medium until induction (OD600 ≈ 0.8–1.0) with 1 mM IPTG, followed by overnight growth at 18 ◦C. Both proteins were purified using FPLC (Bio-Rad) with a Talon cobalt resin (GE) and a Q HP sepharose column (GE). Separate p300 HAT and Sir2 fractions were stored in −80 ◦C until later use. The final storage buffer for p300 HAT is ~150 mM NaCl, 125 mM TCEP, 25% (*v*/*v*) glycerol, 20 mM Tris, pH 8.
