Epigenetic Transcriptional Memory of <i>GAL</i> Genes Depends on Growth in Glucose and the Tup1 Transcription Factor in <i>Saccharomyces cerevisiae</i>

Abstract

Previously expressed inducible genes can remain poised for faster reactivation for multiple cell divisions, a conserved phenomenon called epigenetic transcriptional memory. The <i>GAL</i> genes in <i>Saccharomyces cerevisiae</i> show faster reactivation for up to seven generations after being repressed. During memory, previously produced Gal1 protein enhances the rate of reactivation of <i>GAL1</i>, <i>GAL10</i>, <i>GAL2</i>, and <i>GAL7</i> These genes also interact with the nuclear pore complex (NPC) and localize to the nuclear periphery both when active and during memory. Peripheral localization of <i>GAL1</i> during memory requires the Gal1 protein, a memory-specific <i>cis</i>-acting element in the promoter, and the NPC protein Nup100 However, unlike other examples of transcriptional memory, the interaction with NPC is not required for faster <i>GAL</i> gene reactivation. Rather, downstream of Gal1, the Tup1 transcription factor and growth in glucose promote <i>GAL</i> transcriptional memory. Cells only show signs of memory and only benefit from memory when growing in glucose. Tup1 promotes memory-specific chromatin changes at the <i>GAL1</i> promoter: incorporation of histone variant H2A.Z and dimethylation of histone H3, lysine 4. Tup1 and H2A.Z function downstream of Gal1 to promote binding of a preinitiation form of RNA Polymerase II at the <i>GAL1</i> promoter, poising the gene for faster reactivation. This mechanism allows cells to integrate a previous experience (growth in galactose, reflected by Gal1 levels) with current conditions (growth in glucose, potentially through Tup1 function) to overcome repression and to poise critical <i>GAL</i> genes for future reactivation.