Transcriptional and epigenetic regulation of ncx1 and ncx3 in the brain

• Published in: Cell calcium (Edinburgh) 2020-05, Vol.87, p.102194-102194, Article 102194
• Main Authors: Formisano, Luigi, Guida, Natascia, Mascolo, Luigi, Serani, Angelo, Laudati, Giusy, Pizzorusso, Vincenzo, Annunziato, Lucio
• Format: Article
• Language: English
• Subjects: Cerebral ischemia; Epigenetic; Neurodegeneration
• ISSN: 0143-4160; 1532-1991
• DOI: 10.1016/j.ceca.2020.102194

[Display omitted] •NCX1 is down-regulated after stroke through epigenetic mechanisms involving the REST/Sp3/HDAC1/HDAC2 complex and miR-103-1.•NCX3 is down-regulated after stroke through epigenetic mechanisms involving DREAM/HDAC4/HDAC5 complex.•NCX1 is epigenetically up-regulated after brain ischemic preconditioning through the HIF-1/Sp1/p300 complex. Sodium-calcium exchanger (NCX) 1 and 3, have been demonstrated to play a relevant role in controlling the intracellular homeostasis of sodium and calcium ions in physiological and patho-physiological conditions. While NCX1 and NCX3 knocking-down have been both implicated in brain ischemia, several aspects of the epigenetic regulation of these two antiporters transcription were not yet well characterized. In response to stroke, NCX1 and NCX3 transcriptional regulation occurs from specific promoter sequences. Several evidences have shown that the expression of NCX1 and NCX3 can be determined by epigenetic modifications, consisting in changes of the histone acetylation levels on their promoter sequences. An interesting issue is that histone modifications at the NCX1 and NCX3 promoters could be linked to neurodegeneration occurring after stroke. Therefore, identifying the epigenetic regulation at the NCX1 and NCX3 promoters could permit to identify new molecular targets that can open new strategies for stroke treatment. The current review reassumes the recent knowledge of histone modifications of NCX1 and NCX3 genes in brain in physiological and patho-physiological conditions.