Abstract
Mitochondrial carriers catalyse the translocation of numerous metabolites across the inner mitochondrial membrane, playing a key role in different cell functions. For this reason, mitochondrial carrier gene expression needs tight regulation. The human SLC25A13 gene, encoding for the mitochondrial aspartate/glutamate carrier isoform 2 (AGC2), catalyses the electrogenic exchange of aspartate for glutamate plus a proton, thus taking part in many metabolic processes including the malate-aspartate shuttle. By the luciferase (LUC) activity of promoter deletion constructs we identified the putative promoter region, comprising the proximal promoter (−442 bp/−19 bp), as well as an enhancer region (−968 bp/−768 bp). Furthermore, with different approaches, such as in silico promoter analysis, gene silencing and chromatin immunoprecipitation, we identified two transcription factors responsible for SLC25A13 transcriptional regulation: FOXA2 and USF1. USF1 acts as a positive transcription factor which binds to the basal promoter thus ensuring SLC25A13 gene expression in a wide range of tissues. The role of FOXA2 is different, working as an activator in hepatic cells. As a tumour suppressor, FOXA2 could be responsible for SLC25A13 high expression levels in liver and its downregulation in hepatocellular carcinoma (HCC).
Document Type
Article
Publication Date
4-16-2019
Digital Object Identifier (DOI)
https://doi.org/10.3390/ijms20081888
Funding Information
This research was supported by Grants from University of Basilicata to VI (grant number 3010101) and to ST (grant number 102050101), University of Bari (grant number 00405815).
Related Content
Supplementary materials can be found at https://www.mdpi.com/1422-0067/20/8/1888/s1.
Repository Citation
Convertini, Paolo; Todisco, Simona; De Santis, Francesco; Pappalardo, Ilaria; Iacobazzi, Dominga; Castiglione Morelli, Maria Antonietta; Fondufe-Mittendorf, Yvonne N.; Martelli, Giuseppe; Palmieri, Ferdinando; and Infantino, Vittoria, "Transcriptional Regulation Factors of the Human Mitochondrial Aspartate/Glutamate Carrier Gene, Isoform 2 (SLC25A13): USF1 as Basal Factor and FOXA2 as Activator in Liver Cells" (2019). Molecular and Cellular Biochemistry Faculty Publications. 165.
https://uknowledge.uky.edu/biochem_facpub/165
Supplementary Materials
Notes/Citation Information
Published in International Journal of Molecular Sciences, v. 20, issue 8, 1888, p. 1-16.
© 2019 by the authors. Licensee MDPI, Basel, Switzerland.
This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).