Epigenetics, chromatin remodeling in cellular quiescence and cancer

The goal of this 5-year project is to understand the specific functions of chromatin remodeling factors in cellular quiescence and cancer.

Cellular quiescence is a reversible differentiation state when cells are reducing the metabolic functions to adapt to a new environment.

It is clear that epigenetic changes are important in cellular quiescence and cancer, however the specific roles of chromatin remodeling factors have not been well defined.We will use fission yeast cells and immortalized human fibroblasts as cellular and genetic model systems to specify the functions of two chromatin remodeling factors in quiescence.

Our previous work shows that the RNA polymerase associated factor, Paf1C, and Ino80 (Inositol requiring nucleosome remodeling factor) both contribute to key chromatin changes during this transition.

Epigenetic modifications and gene expression changes will be mapped using genome-wide methodologies in both model systems.

The proposed project will determine the mechanistic functions of Paf1C and Ino80 and their specific roles in regulation of gene expression during quiescence. In addition, Paf1C has a known oncogenic role in lung cancer cells that we will plan to further investigate. The project is medically important since quiescent cancer cells are generally resistant to chemotherapy.

Therefore, understanding how remodeling factors are controlling chromatin changes during the transition from proliferation to quiescence will be important for future therapies.