title: SET1 and p300 act synergistically, through coupled histone modifications, in transcriptional activation by p53.
abstract: The H3K4me3 mark in chromatin is closely correlated with actively transcribed genes, although the mechanisms involved in its generation and function are not fully understood. In vitro studies with recombinant chromatin and purified human factors demonstrate a robust SET1 complex (SET1C)-mediated H3K4 trimethylation that is dependent upon p53- and p300-mediated H3 acetylation, a corresponding SET1C-mediated enhancement of p53- and p300-dependent transcription that reflects a primary effect of SET1C through H3K4 trimethylation, and direct SET1C-p53 and SET1C-p300 interactions indicative of a targeted recruitment mechanism. Complementary cell-based assays demonstrate a DNA-damage-induced p53-SET1C interaction, a corresponding enrichment of SET1C and H3K4me3 on a p53 target gene (p21/WAF1), and a corresponding codependency of H3K4 trimethylation and transcription upon p300 and SET1C. These results establish a mechanism in which SET1C and p300 act cooperatively, through direct interactions and coupled histone modifications, to facilitate the function of p53.
authors.affiliation: Laboratory of Biochemistry and Molecular Biology, The Rockefeller University, New York, NY 10065, USA.
authors.forename: Zhanyun
authors.initials: Z
authors.lastname: Tang
authors.forename: Wei-Yi
authors.initials: WY
authors.lastname: Chen
authors.forename: Miho
authors.initials: M
authors.lastname: Shimada
authors.forename: Uyen T T
authors.initials: UT
authors.lastname: Nguyen
authors.forename: Jaehoon
authors.initials: J
authors.lastname: Kim
authors.forename: Xiao-Jian
authors.initials: XJ
authors.lastname: Sun
authors.forename: Toru
authors.initials: T
authors.lastname: Sengoku
authors.forename: Robert K
authors.initials: RK
authors.lastname: McGinty
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Fernandez
authors.forename: Tom W
authors.initials: TW
authors.lastname: Muir
authors.forename: Robert G
authors.initials: RG
authors.lastname: Roeder
mesh_terms: D000107:Acetylation; D000595:Amino Acid Sequence; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D004249:DNA Damage; D050881:E1A-Associated p300 Protein / Q000378:metabolism*; D045325:HCT116 Cells; D042421:Histone Code; D011495:Histone-Lysine N-Methyltransferase / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D006801:Humans; D008745:Methylation; D008969:Molecular Sequence Data; D046912:Multiprotein Complexes / Q000378:metabolism; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D006657:Histones; D046912:Multiprotein Complexes; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D011495:Histone-Lysine N-Methyltransferase; C526068:Setd1A protein, human; D050881:E1A-Associated p300 Protein; C494360:EP300 protein, human