title: Mechanism of retinoic acid-induced transcription: histone code, DNA oxidation and formation of chromatin loops.
abstract: Histone methylation changes and formation of chromatin loops involving enhancers, promoters and 3' end regions of genes have been variously associated with active transcription in eukaryotes. We have studied the effect of activation of the retinoic A receptor, at the RARE-promoter chromatin of CASP9 and CYP26A1 genes, 15 and 45 min following RA exposure, and we found that histone H3 lysines 4 and 9 are demethylated by the lysine-specific demethylase, LSD1 and by the JMJ-domain containing demethylase, D2A. The action of the oxidase (LSD1) and a dioxygenase (JMJD2A) in the presence of Fe++ elicits an oxidation wave that locally modifies the DNA and recruits the enzymes involved in base and nucleotide excision repair (BER and NER). These events are essential for the formation of chromatin loop(s) that juxtapose the RARE element with the 5' transcription start site and the 3' end of the genes. The RARE bound-receptor governs the 5' and 3' end selection and directs the productive transcription cycle of RNA polymerase. These data mechanistically link chromatin loops, histone methylation changes and localized DNA repair with transcription.
authors.affiliation: Dipartimento di Biologia, Università Federico II, 80126 Napoli, Italy.
authors.forename: Candida
authors.initials: C
authors.lastname: Zuchegna
authors.affiliation: Dipartimento di Medicina e di Scienze della Salute, Università del Molise, 86100 Campobasso, Italy.
authors.forename: Fabiana
authors.initials: F
authors.lastname: Aceto
authors.affiliation: Dipartimento di Medicina Molecolare e Biotecnologie mediche, Istituto di Endocrinologia ed Oncologia Sperimentale del C.N.R., Università Federico II, 80131 Napoli, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Bertoni
authors.affiliation: Dipartimento di Biologia, Università Federico II, 80126 Napoli, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Romano
authors.affiliation: Istituto di Scienze dell'Alimentazione, C.N.R., 83100 Avellino, Italy.
authors.forename: Bruno
authors.initials: B
authors.lastname: Perillo
authors.affiliation: Dipartimento di Biologia, Università Federico II, 80126 Napoli, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Laccetti
authors.affiliation: Institute of Cancer Research, Columbia University Medical Center, New York, NY 10032, USA.
authors.forename: Max E
authors.initials: ME
authors.lastname: Gottesman
authors.affiliation: Dipartimento di Medicina Molecolare e Biotecnologie mediche, Istituto di Endocrinologia ed Oncologia Sperimentale del C.N.R., Università Federico II, 80131 Napoli, Italy antonio.porcellini@unina.it.
authors.forename: Enrico V
authors.initials: EV
authors.lastname: Avvedimento
authors.affiliation: Dipartimento di Biologia, Università Federico II, 80126 Napoli, Italy antonio.porcellini@unina.it.
authors.forename: Antonio
authors.initials: A
authors.lastname: Porcellini
mesh_terms: D053453:Caspase 9 / Q000235:genetics; D002843:Chromatin / Q000737:chemistry* / Q000187:drug effects / Q000201:enzymology; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D004247:DNA / Q000378:metabolism; D045643:DNA Repair Enzymes / Q000378:metabolism; D042421:Histone Code / Q000187:drug effects; D056466:Histone Demethylases / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D006801:Humans; D061986:MCF-7 Cells; D008745:Methylation / Q000187:drug effects; D010084:Oxidation-Reduction; D011401:Promoter Regions, Genetic; D012319:RNA Polymerase II / Q000378:metabolism; D018168:Receptors, Retinoic Acid / Q000378:metabolism; D000072516:Retinoic Acid 4-Hydroxylase; D014158:Transcription, Genetic / Q000187:drug effects; D014212:Tretinoin / Q000494:pharmacology*
chemical_list: D002843:Chromatin; D006657:Histones; D018168:Receptors, Retinoic Acid; D014212:Tretinoin; D004247:DNA; D003577:Cytochrome P-450 Enzyme System; D056466:Histone Demethylases; D000072516:Retinoic Acid 4-Hydroxylase; D012319:RNA Polymerase II; D053453:Caspase 9; D045643:DNA Repair Enzymes