Sip4, a Snf1 kinase-dependent transcriptional activator, binds to the carbon source-responsive element of gluconeogenic genes

The carbon source-responsive element (CSRE) mediates transcriptional activation of the gluconeogenic genes during growth of the yeast Saccharomyces cerevisiae on non-fermentable carbon sources. Previous studies have suggested that the Cats protein activates the expression of CSRE-binding factors. We show here that one of these factors is Sip4, a glucose-regulated C-6 zinc cluster activator which was identified by its interaction with the Snf1 protein kinase. We present genetic evidence that Sip4 contributes to transcriptional activation by the CSRE and biochemical evidence that Sip4 binds to the CSRE. Binding was detected in electrophoretic mobility shift assays with both yeast nuclear extracts and a bacterially expressed Sip4 fusion protein. Evidence suggests that Sip4 also activates the expression of other CSRE-binding proteins. Finally, we show that Cats regulates SIP4 expression and that overexpression of Sip4 compensates for loss of Cats. We propose a model for activation by the CSRE in which Sip4 and Cats have related functions, but Cats is the primary regulator because it controls Sip4 expression.