This study investigates the transcriptional role of the human mitochondrial carnitine/acylcarnitine carrier (CAC) proximal promoter. Through deletion analysis, an activation domain (334/80 bp) was identified which contains FOXA and Sp1 active sites. The wild-type (but not mutated) 334/80 bp region of the CAC gene conferred 74% LUC transgene activity in HepG2 cells, 17% in HEK293 cells and 14% in SK-NSH cells as compared to that observed with the entire 1503/+3 bp proximal promoter. Overexpression and silencing of FOXA2 or Sp1 in HepG2 cells enhanced and diminished, respectively, LUC activity, CAC transcript and CAC protein. In HEK293 and SK-N-SH cells, which do not contain FOXA1-3, LUC activity was increased by FOXA2 overexpression to a greater extent than in HepG2 cells. Both FOXA2 and Sp1 in HepG2, and only Sp1 in HEK293 and SK-N-SH cells, were found to be bound to the CAC proximal promoter. These results show that FOXA and Sp1 sites in HepG2 cells and only the Sp1 site in HEK293 and SK-N-SH cells have a critical role in the transcriptional regulation of the CAC proximal promoter.

Role of FOXA and Sp1 in mitochondrial acylcarnitine carrier gene expression in different cell lines

IACOBAZZI, Vito
2011-01-01

Abstract

This study investigates the transcriptional role of the human mitochondrial carnitine/acylcarnitine carrier (CAC) proximal promoter. Through deletion analysis, an activation domain (334/80 bp) was identified which contains FOXA and Sp1 active sites. The wild-type (but not mutated) 334/80 bp region of the CAC gene conferred 74% LUC transgene activity in HepG2 cells, 17% in HEK293 cells and 14% in SK-NSH cells as compared to that observed with the entire 1503/+3 bp proximal promoter. Overexpression and silencing of FOXA2 or Sp1 in HepG2 cells enhanced and diminished, respectively, LUC activity, CAC transcript and CAC protein. In HEK293 and SK-N-SH cells, which do not contain FOXA1-3, LUC activity was increased by FOXA2 overexpression to a greater extent than in HepG2 cells. Both FOXA2 and Sp1 in HepG2, and only Sp1 in HEK293 and SK-N-SH cells, were found to be bound to the CAC proximal promoter. These results show that FOXA and Sp1 sites in HepG2 cells and only the Sp1 site in HEK293 and SK-N-SH cells have a critical role in the transcriptional regulation of the CAC proximal promoter.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11586/9916
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