Snf1, the yeast AMP kinase homolog, is essential for derepression of glucose-repressed genes that are activated by Adr1. Although required for Adr1 DNA binding, the precise role of Snf1 is unknown. Deletion of histone deacetylase genes allowed constitutive promoter binding of Adr1 and Cat8, another activator of glucose-repressed genes. In repressed conditions, at the Adr1-and Cat8-dependent ADH2 promoter, partial chromatin remodeling had occurred, and the activators recruited a partial preinitiation complex that included RNA polymerase II. Transcription did not occur, however, unless Snf1 was activated, suggesting a Snf1-dependent event that occurs after RNA polymerase II recruitment. Glucose regulation persisted because shifting to low glucose increased expression. Glucose repression could be completely relieved by combining the three elements of 1) chromatin perturbation by mutation of histone deacetylases, 2) activation of Snf1, and 3) the addition of an Adr1 mutant that by itself confers only weak constitutive activity.The general model for eukaryotic transcription activation is that a preinitiation complex forms by ordered recruitment of specific and general transcription factors to a promoter (see reviews in Refs. 1-3). Early in activation, promoter-specific factors bind, possibly with the aid of general chromatin remodeling factors (4, 5). Bound activators recruit coactivators including histone modifiers and chromatin remodeling complexes such as SAGA 2 or SWI/SNF. The resulting alterations to chromatin and interactions between bound activator, Mediator complex, and general transcription factors ultimately leads to the recruitment of TBP and RNA Pol II (5-7).Although the model implies transcription when all components of the preinitiation complex are in place, several cases are known in which Pol II is recruited to a promoter but does not proceed through the open reading frame without an additional signal (8 -10). The classic example is the Drosophila hsp70 heat shock gene. In the absence of an activating heat shock and with very little bound heat shock factor, Pol II binds the promoter and initiates transcription, only to pause ϳ25 nucleotides from the initiation site. Within seconds after heat shock, additional heat shock factor binds, elongation proceeds through the open reading frame (11), and more Pol II is recruited (10). This mechanism allows for a rapid transcriptional response to a potentially lethal environmental challenge.Reacting to a change in carbon source does not have the urgency of responding to heat shock, and activation of the glucose-repressed genes does not involve a paused polymerase (see review of glucose repression in Ref. 12). We have, however, detected a polymerase complex bound to a glucose-repressed promoter in a strain deleted for the histone deacetylase (HDAC) genes, HDA1 and RPD3. In HDAC mutants, the Adr1 and Cat8 activators, which normally bind to glucose-repressed promoters only in low glucose conditions, bound constitutively. SNF1, which encodes the yeast AMP kinase homo...