Upstream stimulatory factor 1 transactivates the human gene promoter of the cardiac isoform of acetyl-CoA carboxylase

E-box cis-elements act as binding sites for upstream stimulatory factors (USFs), putative glucose-responsive transcriptional modulators. Since four E-boxes were identified on the human ACCβ promoter, we hypothesized that USF1 induces ACCβ expression in a glucose-dependent manner. Here, murine cardiac ACCβ expression was significantly increased in response to high carbohydrate re-feeding after fasting. However, transfection studies showed no difference in ACCβ promoter activity in neonatal cardiomyocytes and CV-1 fibroblasts after low (5.5 mM) and high (25 mM) glucose exposure. USF1 overexpression significantly increased ACCβ promoter activity in both cell lines under low glucose conditions. With high glucose exposure, USF1 further induced ACCβ promoter activity only in CV-1 fibroblasts. USF1-induced ACCβ promoter responsiveness was markedly attenuated when cotransfecting cardiomyocytes with a −93/+65 or −38/+65 promoter deletion construct (lacking E-boxes 1–3). Thus, USF1 transactivates the human ACCβ promoter in the heart, likely through an E-box cis-element located close to the transcription start site.