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Oxford University Press, Nucleic Acids Research, 19(42), p. 12329-12329, 2014

DOI: 10.1093/nar/gku958

Oxford University Press, Nucleic Acids Research, 17(42), p. 11040-11055, 2014

DOI: 10.1093/nar/gku823

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Mechanism of retinoic acid-induced transcription: histone code, DNA oxidation and formation of chromatin loops

Journal article published in 2014 by Candida Zuchegna, Fabiana Aceto, Alessandra Bertoni, Antonella Romano, Bruno Perillo, Paolo Laccetti, Max E. Gottesman, Enrico V. Avvedimento, Antonio Porcellini ORCID
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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Abstract

Histone methylation changes and formation of chro- matin loops involving enhancers, promoters and 3′ end regions of genes have been variously associ- ated with active transcription in eukaryotes. We have studied the effect of activation of the retinoic A re- ceptor, at the RARE–promoter chromatin of CASP9 and CYP26A1 genes, 15 and 45 min following RA ex- posure, and we found that histone H3 lysines 4 and 9 are demethylated by the lysine-specific demethylase, LSD1 and by the JMJ-domain containing demethy- lase, D2A. The action of the oxidase (LSD1) and a dioxygenase (JMJD2A) in the presence of Fe++ elic- its an oxidation wave that locally modifies the DNA and recruits the enzymes involved in base and nu- cleotide excision repair (BER and NER). These events are essential for the formation of chromatin loop(s) that juxtapose the RARE element with the 5′ tran- scription start site and the 3′ end of the genes. The RARE bound-receptor governs the 5′ and 3′ end se- lection and directs the productive transcription cycle of RNA polymerase. These data mechanistically link chromatin loops, histone methylation changes and localized DNA repair with transcription.