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.

Public Health Relevance

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.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM118712-02
Application #
9310277
Study Section
Nuclear and Cytoplasmic Structure/Function and Dynamics Study Section (NCSD)
Program Officer
Carter, Anthony D
Project Start
2016-08-01
Project End
2020-07-31
Budget Start
2017-08-01
Budget End
2018-07-31
Support Year
2
Fiscal Year
2017
Total Cost
Indirect Cost
Name
Northwestern University at Chicago
Department
Biochemistry
Type
Schools of Arts and Sciences
DUNS #
160079455
City
Evanston
State
IL
Country
United States
Zip Code
60201
D'Urso, Agustina; Brickner, Jason H (2017) Epigenetic transcriptional memory. Curr Genet 63:435-439
Satomura, Atsushi; Brickner, Jason H (2017) Nuclear Pore Complexes: A Scaffold Regulating Developmental Transcription? Trends Cell Biol 27:621-622
Brickner, Jason (2017) Genetic and epigenetic control of the spatial organization of the genome. Mol Biol Cell 28:364-369
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