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 ACCbeta promoter, we hypothesized that USF1 induces ACCbeta expression in a glucose-dependent manner. Here, murine cardiac ACCbeta expression was significantly increased in response to high carbohydrate re-feeding after fasting. However, transfection studies showed no difference in ACCbeta promoter activity in neonatal cardiomyocytes and CV-1 fibroblasts after low (5.5mM) and high (25 mM) glucose exposure. USF1 overexpression significantly increased ACCbeta promoter activity in both cell lines under low glucose conditions. With high glucose exposure, USF1 further induced ACCbeta promoter activity only in CV-1 fibroblasts. USF1-induced ACCbeta promoter responsiveness was markedly attenuated when co-transfecting cardiomyocytes with a -93/+65 or -38/+65 promoter deletion construct (lacking E-boxes 1-3). Thus, USF1 transactivates the human ACCbeta promoter in the heart, likely through an E-box cis-element located close to the transcription start site.
Makaula
Siyanda
S
Hatter Heart Research Institute, University of Cape Town Faculty of Health Sciences, Observatory 7925, South Africa.
Adam
Tasneem
T
Essop
M Faadiel
MF
D000103:Acetyl-CoA Carboxylase / Q000378:metabolism*; D000821:Animal Feed; D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D005215:Fasting; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D051379:Mice; D032383:Myocytes, Cardiac / Q000166:cytology / Q000201:enzymology; D011401:Promoter Regions, Genetic / Q000502:physiology*; D020033:Protein Isoforms / Q000737:chemistry / Q000378:metabolism; D015533:Transcriptional Activation; D051720:Upstream Stimulatory Factors / Q000502:physiology*
D020033:Protein Isoforms; D051720:Upstream Stimulatory Factors; C497183:Usf1 protein, mouse; D000103:Acetyl-CoA Carboxylase; D005947:Glucose