The molecular mechanisms and functional significance of gene positioning

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Project Summary Understanding the molecular control of transcriptional responses of cells to environmental signals is essential to understand how environment, aging and lifestyle impact physiology. My lab has discovered that the position of genes is actively controlled by cells and that this impacts transcription in several ways. Although we study this phenomenon in the simple budding yeast, it is conserved to more complex animals, including humans. We recently showed that a majority of transcription factors control the interaction of genes with the Nuclear Pore Complex (NPC), impacting the spatial arrangement of genes and the interaction of chromosomes. Furthermore, we have shown that this interaction with the NPC can either promote stronger transcription and alter chromatin structure to poise genes for future expression. Thus, transcription factor-mediated targeting to the NPC likely has broad effects on both the spatial organization of the genome and gene expression. The goals of this work are to determine the molecular mechanisms by which transcription factors and NPCs spatially arrange the yeast genome and to understand how these interactions impact gene expression and chromatin structure.