Mascolo, Luigi (2018) Identification of Epigenetic Mechanisms Regulating NCX3 in in Vivo Model of Brain Ischemic Preconditioning. [Tesi di dottorato]
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| Item Type: | Tesi di dottorato |
|---|---|
| Resource language: | English |
| Title: | Identification of Epigenetic Mechanisms Regulating NCX3 in in Vivo Model of Brain Ischemic Preconditioning |
| Creators: | Creators Email Mascolo, Luigi mascololuigi88@gmail.com |
| Date: | 11 December 2018 |
| Number of Pages: | 86 |
| Institution: | Università degli Studi di Napoli Federico II |
| Department: | Neuroscienze e Scienze Riproduttive ed Odontostomatologiche |
| Dottorato: | Neuroscienze |
| Ciclo di dottorato: | 31 |
| Coordinatore del Corso di dottorato: | nome email Taglialatela, Maurizio mtaglial@unina.it |
| Tutor: | nome email Formisano, Luigi UNSPECIFIED |
| Date: | 11 December 2018 |
| Number of Pages: | 86 |
| Keywords: | ischemic insult;stroke;GATA3;histone 3 lysine 3 trimethylation;KMT2A; |
| Settori scientifico-disciplinari del MIUR: | Area 05 - Scienze biologiche > BIO/14 - Farmacologia |
| Date Deposited: | 19 Dec 2018 11:32 |
| Last Modified: | 22 Jun 2020 09:15 |
| URI: | http://www.fedoa.unina.it/id/eprint/12677 |
Collection description
Variations of the isoform 3 expression of the sodium / calcium exchanger play an important role in the response to neuronal damage after an ischemic insult. I found that the transcription factor (GATA binding protein) 3 GATA3 activates the transcription of ncx3 in rat cortical cultures. In fact, the overexpression of GATA3, obtained as a result of transient transfection of the plasmid containing the GATA3 cDNA in neurons, leads to a significant increase in the luciferase activity of the ncx3 promoter, in parallel with an increase in mRNA and protein expression of ncx3. In contrast, the transfection of a siRNA capable of reducing the protein expression of GATA3 by about 60% causes a reduction of the luciferase activity of the ncx3 promoter and a decrease in the ncx3 mRNA. The site-specific mutagenesis of the binding sequence of GATA3 on the ncx3 promoter demonstrates that the mechanism by which GATA3 activates NCX3 is site-specific. More important, in vivo, GATA3 recruitment to the ncx3 gene was increased in the temporoparietal cortex of rats subjected to Preconditioning (PC) followed by transient middle cerebral artery occlusion (tMCAO), with an increase of histone 3 lysine 3 trimethylation of the ncx3 promoter region. Interestingly, in the same experimental conditions histone acetylation on ncx3 promoter was unmodified. Furthermore, Re-ChIP experiments demonstrated that GATA3 forms a functional complex with the histone lysine methyl transferase KMT2A on the ncx3 gene during PC+tMCAO. Therefore, increasing KMT2A expression or activity might represent a new possible strategy in stroke intervention.
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