Zuchegna, Candida (2014) Mechanism of retinoic acid-induced transcription: histone code, DNA oxidation and formation of chromatin loops. [Tesi di dottorato]


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Item Type: Tesi di dottorato
Resource language: English
Title: Mechanism of retinoic acid-induced transcription: histone code, DNA oxidation and formation of chromatin loops
Zuchegna, Candidacandida.zuchegna@alice.it
Date: 30 March 2014
Number of Pages: 106
Institution: Università degli Studi di Napoli Federico II
Department: Medicina Molecolare e Biotecnologie Mediche
Scuola di dottorato: Medicina molecolare
Dottorato: Patologia e fisiopatologia molecolare
Ciclo di dottorato: 26
Coordinatore del Corso di dottorato:
Avvedimento, Vittorio Enricoavvedim@unina.it
Porcellini, AntonioUNSPECIFIED
Date: 30 March 2014
Number of Pages: 106
Keywords: gene loops, histone code, retinoic acid
Settori scientifico-disciplinari del MIUR: Area 05 - Scienze biologiche > BIO/11 - Biologia molecolare
Area 06 - Scienze mediche > MED/04 - Patologia generale
Date Deposited: 10 Apr 2014 13:23
Last Modified: 26 Jan 2015 11:30
URI: http://www.fedoa.unina.it/id/eprint/9829

Collection description

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. It is not known if these events are mechanistically linked and their specific role in transcription initiation. We have studied the effect of activation of the Retinoic A receptor, at the RARE-promoter chromatin of CASP9 and CYP26A1 genes, at 15 and 45 min following RA exposure, and we found that histone H3 lysine 4 and 9 are demethylated by the lysinespecific 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 locally 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. This is the first demonstration that chromatin loops, histone methylation changes and localized DNA repair are mechanistically linked.


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