In yeast and humans, interaction of a nuclear pore protein with promoters alters chromatin structure and allows RNA polymerase II to bind, poising them for faster reactivation for several generations.

In yeast, transcription factors mediate gene positioning at the nuclear periphery and interchromosomal clustering. These phenomena are regulated by several different strategies that lead to dynamic changes in the spatial arrangement of genes over different time scales.

No abstract

“DNA zip codes” control positioning and interchromosomal clustering of GAL1-10 in yeast. However, these two phenomena have distinct molecular mechanisms, requiring different nuclear pore proteins, and are regulated differently by transcription and the cell cycle.

Previously expressed inducible genes can remain poised for faster reactivation for multiple cell divisions, a conserved phenomenon called epigenetic transcriptional memory. The genes in show faster reactivation for up to seven generations after being repressed. During memory, previously produced Gal1 protein enhances the rate of reactivation of ,, , and 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 during memory requires the Gal1 protein, a memory-specific-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 gene reactivation. Rather, downstream of Gal1, the Tup1 transcription factor and growth in glucose promote 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 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 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 genes for future reactivation.