Understanding the molecular basis of epigenetic mechanisms that control the transcriptional response of cells to environmental signals is essential to understand how environment, aging and lifestyle impact physiology. My lab has discovered an evolutionarily conserved mechanism of epigenetically inherited transcriptional memory that involves the interaction of genes with nuclear pore proteins (8-10). Using both the INO1 gene from yeast and interferon ?-inducible genes in HeLa cells as models for transcriptional memory, we find that previously expressed genes interact with nuclear pore proteins for 4- 7 generations and this leads to an altered chromatin structure in the promoters of these genes. This allows RNA polymerase II to bind to these promoters, poising them for re-activation. We have now find that the scope of genes regulated by transcriptional memory includes dozens of stress-induced genes in yeast that utilize the same system. Therefore, transcriptional memory is a universal, ancient and conserved mechanism by which cells can integrate previous experience to affect future physiology. The goals of this work are to determine the molecular mechanisms that control establishment and inheritance of transcriptional memory in yeast and human cells.
Cells respond environmental signals through changes in gene expression. However, the previous experience of a cell can profoundly alter how cells respond to such signals for multiple generations. This project seeks to define the molecular mechanisms by which cells 'remember' previous experiences.
| Sump, Bethany; Brickner, Jason H (2017) Nup98 regulation of histone methylation promotes normal gene expression and may drive leukemogenesis. Genes Dev 31:2201-2203 |
| Satomura, Atsushi; Brickner, Jason H (2017) Nuclear Pore Complexes: A Scaffold Regulating Developmental Transcription? Trends Cell Biol 27:621-622 |
| Sood, Varun; Cajigas, Ivelisse; D'Urso, Agustina et al. (2017) Epigenetic Transcriptional Memory of GAL Genes Depends on Growth in Glucose and the Tup1 Transcription Factor in Saccharomyces cerevisiae. Genetics 206:1895-1907 |
| Brickner, Jason (2017) Genetic and epigenetic control of the spatial organization of the genome. Mol Biol Cell 28:364-369 |
| D'Urso, Agustina; Brickner, Jason H (2017) Epigenetic transcriptional memory. Curr Genet 63:435-439 |
| Sood, Varun; Brickner, Jason H (2017) Genetic and Epigenetic Strategies Potentiate Gal4 Activation to Enhance Fitness in Recently Diverged Yeast Species. Curr Biol 27:3591-3602.e3 |
