title: P/CAF-mediated spermidine acetylation regulates histone acetyltransferase activity.
abstract: Histones and polyamines are important determinants of the chromatin structure. Histones form the core of nucleosome particles and their modification by acetylation of N-terminal tails is involved in chromatin structural changes and transcriptional regulation. Polyamines, including spermidine, are also targets of both cytoplasmic and nuclear acetylation, which in turn alters their affinity for DNA and nucleosomes. Previous studies report the interplay between polyamines metabolism and levels of histone acetylation, but the molecular basis of this effect is still unclear. In this work, we have analyzed the in vitro effect of spermidine on histone H3 acetylation catalyzed by P/CAF, a highly conserved histone acetyltransferase (HAT) (E.C. 2.3.1.48). We have observed that spermidine at very low concentrations activates P/CAF, while it has an inhibitory effect at concentrations higher than 4 μM. In addition, the in vitro bimodal effect of spermidine on histone H3 acetylation was also distinctly observed in vivo on polytene chromosomes of Drosophila melanogaster. We also performed kinetic studies indicating that the activating effect of low spermidine concentrations on P/CAF-HAT activity is based on its involvement as a substrate for P/CAF to produce N8-acetylspermidine that is able in turn to increase the enzyme activity up to four fold.
authors.affiliation: a Istituto Telethon Dulbecco , Palermo , Italy.|b Dipartimento Di Scienze E Tecnologie Biologiche Chimiche E Farmaceutiche (STEBICEF) - Sezione Di Biologia Cellulare, Università Degli Studi Di Palermo , Palermo , Italy.
authors.forename: Giosalba
authors.initials: G
authors.lastname: Burgio
authors.affiliation: a Istituto Telethon Dulbecco , Palermo , Italy.|b Dipartimento Di Scienze E Tecnologie Biologiche Chimiche E Farmaceutiche (STEBICEF) - Sezione Di Biologia Cellulare, Università Degli Studi Di Palermo , Palermo , Italy.
authors.forename: Davide F V
authors.initials: DF
authors.lastname: Corona
authors.affiliation: c Centro Di Oncobiologia Sperimentale (C.OB.S) , Palermo , Italy.
authors.forename: Concetta M A
authors.initials: CM
authors.lastname: Nicotra
authors.affiliation: d ARNAS Civico, Piazza Nicola Leotta , Palermo , Italy , and.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Carruba
authors.affiliation: e Dipartimento Di Biomedicina Sperimentale E Neuroscienze Cliniche (BIONEC), Universitá degli Studi di Palermo , Palermo , Italy.
authors.forename: Gennaro
authors.initials: G
authors.lastname: Taibi
mesh_terms: D000107:Acetylation; D000818:Animals; D004331:Drosophila melanogaster; D004789:Enzyme Activation / Q000187:drug effects; D051548:Histone Acetyltransferases / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D007700:Kinetics; D059007:Polytene Chromosomes / Q000378:metabolism; D013095:Spermidine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D050880:p300-CBP Transcription Factors / Q000378:metabolism*; D000099224:p300-CBP-Associated Factor
chemical_list: D051548:Histone Acetyltransferases; D006657:Histones; D013095:Spermidine; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor
keywords: Histone H3 acetylation; N8-acetylspermidine; P/CAF; apermidine acetylation; spermidine