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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

Research output: Contribution to journalArticle

  • Paolo Convertini
  • Simona Todisco
  • Francesco de Santis
  • Ilaria Pappalardo
  • Dominga Iacobazzi
  • Maria Antonietta Castiglione Morelli
  • Yvonne N Fondufe-Mittendorf
  • Giuseppe Martelli
  • Ferdinando Palmieri
  • Vittoria Infantino
Original languageEnglish
Article number1888
Number of pages16
JournalInternational Journal of Molecular Sciences
Volume20
Issue number8
Early online date16 Apr 2019
DOIs
DateAccepted/In press - 14 Apr 2019
DateE-pub ahead of print - 16 Apr 2019
DatePublished (current) - 30 Apr 2019

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).

    Research areas

  • SLC25A13, AGC2, gene expression, transcriptional regulation, FOXA2, USF1

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    Rights statement: This is the final published version of the article (version of record). It first appeared online via MDPI at https://www.mdpi.com/1422-0067/20/8/1888 . Please refer to any applicable terms of use of the publisher.

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