| In Saccharomyces cerevisiae, many actively transcribed genes localize to the nuclear periphery when they are expressed and a subset of these genes maintain their peripheral localization after repression, facilitating the formation of a novel epigenetic state at the nuclear periphery. The transcription of this "memory" state is markedly different than the naïve state of these memory genes, in a process termed adaptive transcriptional memory. Yet, the molecular mechanism of adaptive transcriptional memory is at best crudely understood in yeast and even less well understood in human cells. To address this, we have used the yeast model gene INO1 to probe the mechanism of yeast adaptive transcriptional memory in terms of cis acting promoter elements, chromatin structure, NPC component interaction and RNAPII association, defining several clear steps to the transcriptional memory of INO1. Using a combination of quantitative chromatin localization and mutagenesis, as well as ChIP and RT-qPCR, we have elucidated several of the keys steps in transcriptional memory, as well as identified multiple chromatin marks required for this epigenetic state. Furthermore, we have determined the conservation of many of these features of transcriptional memory in yeast genes to human genes responsive to interferon-γ, indicating that this behavior in yeast cells is conserved from yeast to humans, shedding new light on this novel regulatory step for gene expression. These results also indicate an additional regulatory step for the differential expression of genes in acquired immunity. |
