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

► An activation domain of CAC gene promoter contains FOXA and Sp1 active sites. ► This domain confers high LUC transgene activity in HepG2 and low activity in HEK293 and SK-N-SH cells. ► FOXA mutations decrease LUC activity in HepG2 but not in HEK293 and SK-N-SH cells not containing FOXA1-3 transcription factors. ► FOXA2 and Sp1 in HepG2 and only Sp1 in HEK293 and SK-N-SH cells are bound to the CAC promoter. ► Our results highlight new mechanisms of CAC gene expression and explain differences in CAC levels between hepatic and non-hepatic cells.