title: Poly(ADP-Ribosyl)ation Affects Histone Acetylation and Transcription.
abstract: Poly(ADP-ribosyl)ation (PARylation) is a posttranslational protein modification catalyzed by members of the poly(ADP-ribose) polymerase (PARP) enzyme family. PARylation regulates a wide variety of biological processes in most eukaryotic cells including energy metabolism and cell death, maintenance of genomic stability, chromatin structure and transcription. Inside the nucleus, cross-talk between PARylation and other epigenetic modifications, such as DNA and histone methylation, was already described. In the present work, using PJ34 or ABT888 to inhibit PARP activity or over-expressing poly(ADP-ribose) glycohydrolase (PARG), we show decrease of global histone H3 and H4 acetylation. This effect is accompanied by a reduction of the steady state mRNA level of p300, Pcaf, and Tnfα, but not of Dnmt1. Chromatin immunoprecipitation (ChIP) analyses, performed at the level of the Transcription Start Site (TSS) of these four genes, reveal that changes in histone acetylation are specific for each promoter. Finally, we demonstrate an increase of global deacetylase activity in nuclear extracts from cells treated with PJ34, whereas global acetyltransferase activity is not affected, suggesting a role for PARP in the inhibition of histone deacetylases. Taken together, these results show an important link between PARylation and histone acetylation regulated transcription.
authors.affiliation: Istituto di Biologia e Patologia Molecolari, CNR c/o Dipartimento di Biologia e Biotecnologie, Sapienza Università di Roma, Rome, Italy.
authors.forename: Loredana
authors.initials: L
authors.lastname: Verdone
authors.affiliation: Ludwig Maximilians University Munich, Planegg-Martinsried, Germany.
authors.forename: Marco
authors.initials: M
authors.lastname: La Fortezza
authors.affiliation: Dipartimento di Biotecnologie Cellulari ed Ematologia, Sapienza Università di Roma, Rome, Italy.|Istituto Pasteur-Fondazione Cenci Bolognetti, Rome, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Ciccarone
authors.affiliation: Dipartimento di Biotecnologie Cellulari ed Ematologia, Sapienza Università di Roma, Rome, Italy.|Istituto Pasteur-Fondazione Cenci Bolognetti, Rome, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Caiafa
authors.affiliation: Dipartimento di Biotecnologie Cellulari ed Ematologia, Sapienza Università di Roma, Rome, Italy.|Istituto Pasteur-Fondazione Cenci Bolognetti, Rome, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Zampieri
authors.affiliation: Istituto di Biologia e Patologia Molecolari, CNR c/o Dipartimento di Biologia e Biotecnologie, Sapienza Università di Roma, Rome, Italy.
authors.forename: Micaela
authors.initials: M
authors.lastname: Caserta
mesh_terms: D000107:Acetylation; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000096:biosynthesis; D050881:E1A-Associated p300 Protein / Q000096:biosynthesis; D042822:Genomic Instability; D006657:Histones / Q000378:metabolism*; D051379:Mice; D041681:NIH 3T3 Cells; D010616:Phenanthrenes / Q000494:pharmacology; D011064:Poly Adenosine Diphosphate Ribose / Q000378:metabolism*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D050880:p300-CBP Transcription Factors / Q000096:biosynthesis; D000099224:p300-CBP-Associated Factor
chemical_list: D001562:Benzimidazoles; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; D050881:E1A-Associated p300 Protein; D006657:Histones; D010616:Phenanthrenes; D011064:Poly Adenosine Diphosphate Ribose; D011065:Poly(ADP-ribose) Polymerases; D014409:Tumor Necrosis Factor-alpha; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor; C434926:N-(oxo-5,6-dihydrophenanthridin-2-yl)-N,N-dimethylacetamide hydrochloride; C521013:veliparib; C000619381:Dnmt1 protein, mouse; C494361:Ep300 protein, mouse