进修班2011-2.pptVIP

北京大学医学部 生化与分子生物学系 HDAC inhibitor (depsipeptide) induces p53 acetylation FoxO1 posttranslational modification and localization Bisulfite sequence for diferent genes L Wu., Mol Cell Biol., 2008 Bisulfite sequence for diferent cell lines Depsipeptide induces a decrease in DNMT1 binding to the p16 promoter H3K9 methylations are decreased in response to depsipeptide treatment WB ChIP Activity of G9a and SUV39H1 is decreased in response to depsipeptide Wu L., et al., Mol Cell Biol., 2008 HDAC inhibitor reduction of SUV39 and G9A reduction of H3K9 methylation reduction of HP1 to histone Decrease in recruitment of DNMT1 to the p16 promoter DNA demethylation Three Basic Classes of HDAC Class?I HDACs?1, 2, 3 and 8 homologs of the yeast RPD3 protein Class?II HDACs?4, 5, 6, 7, 9,10?and 11 homologs of the yeast Hda?1 protein Class III Sirt 1-7 homologs of the yeast Sir2 protein We are recently focusing HDAC III members Sirtuins family proteins in mammalian cells Haigis. M and Guarente L. Genes Dev 2006 Anthony A. Sauve et al. Annu. Rev. Biochem. 2006 Interaction of SIRT1 and non-histone proteins Christopher L. Brooks and Wei Gu Nature Reviews Cancer 2009 Crosstalk between SIRT1 and non-histone proteins SIRT1 and p53 Luo J., et al., Cell, 2001 Vaziri H, et al., Cell, 2001 K382 of p53 is catalyzed by SIRT1 p53 acetylation on C-terminus SET7/9 is a histone methyltransferase on H3K4 Wang H., Mol Cell., 2001 SET7/9 and p53 Regulation of p53 activity through lysine methylation SET7/9 p53 p53 CH3 at K372 Acetylation at K382 CH3 at K372 p21 Chuikov S., Nature, 2004 Interaction between SIRT1 and p53 is regulated by SET7/9 SET7/9 regulates p53 activity even p53K372 mutated (HCT116 -/- cells) p21 expression in p53 WT or p53K372R in response to DNA damage Liu X, PNAS, 2011 SET7/9-induced p53 acetylation is via SIRT1 Interaction of SIRT1 and SET7/9 i