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

Role of FOXA and Sp1 in mitochondrial acylcarnitine carrier gene expression in different cell lines,10.1016/j.bbrc.2010.11.126,Biochemical and Biophys

Role of FOXA and Sp1 in mitochondrial acylcarnitine carrier gene expression in different cell lines   (Citations: 2)
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This study investigates the transcriptional role of the human mitochondrial carnitine/acylcarnitine carrier (CAC) proximal promoter. Through deletion analysis, an activation domain (−334/−80bp) was identified which contains FOXA and Sp1 active sites. The wild-type (but not mutated) −334/−80bp region of the CAC gene conferred 74% LUC transgene activity in HepG2 cells, 17% in HEK293 cells and 14% in SK-N-SH cells as compared to that observed with the entire −1503/+3bp 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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