Sp1 mediates glucose activation of the acetyl-CoA carboxylase promoter

Abstract

Acetyl-CoA carboxylase (ACC), the rate-limiting enzyme in the biosynthesis of fatty acids, is induced in the presence of high glucose levels. The ACC gene contains two promoters: promoter I (PI) expression is inducible under lipogenic conditions, while promoter II (PII) expression, even though constitutively expressed in all tissues, is also controlled under various physiological conditions. Examination of the expression pattern of a series of deletion constructs of PII showed that the region from -340 to -249 was essential for ACC induction. In addition, by electrophoretic mobility shift assays, supershift assays, and DNase I footprinting studies, we have detected the binding of the transcription factor Sp1 at the two GC-rich sequences located within the -340 to -249 region of promoter II. Mutations at the GC- rich sequences prevented binding of Sp1, and the induction of the PII promoter was no longer observed. Cotransfection studies, in Drosophila Schneider SL2 cells, with the Sp1 expression vector and PII-CAT constructs, have further confirmed the activation of promoter II by Sp1. In addition, we have identified Sp3, another member of the Sp1 family of transcription factors, as a second factor that can bind to the glucose response elements of PII.