FOXA transcription factors determine the amplitude of glucocorticoid induction of tyrosine aminotransferase in mice

Bryzgalov, L. O.; Ershov, Nikita I.; Ilnitskaya, S. I.

doi:10.1007/s10517-007-0415-1

Cited by 1 publication

(1 citation statement)

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“…In fact, several genes encoding hepatic enzymes involved in metabolism during fasting and energy deprivation contain FOXA2-binding sites [51,52,53]. Examples include the gluconeogenic enzymes phosphoenopyruvate carboxychinase (PepCk) [54], glucose-6-phosphatase (G6pc) [55] and tyrosine aminotransferase (Tat) [56], as well as enzymes of lipid catabolism, such as carnitine palmitoyltransferase 1, carnitine acylcarnitine translocase, hydroxyacyl-CoA dehydrogenase and lipoprotein lipase and of ketogenesis, such as 3-hydroxy-3-methylglutaryl-CoA synthase 1 [24,50]. Our results further suggest that FOXA2 does not contribute to SLC25A13 gene expression in some non-hepatic cells, such as SK-N-SH cells.…”

Section: Discussionmentioning

confidence: 99%

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

Convertini

Todisco

Santis

et al. 2019

IJMS

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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).

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