Identification of genes modifying epigenetic plasticity during follicle cell differentiation. Ming-Chia Lee1, Andrew Skora2, Allan Spradling1. 1) Department of Embryology, Carnegie Institution of Washington, Baltimore, MD; 2) Ludwig Center for Cancer Genomics and Therapeutics, Johns Hopkins School of Medicine, Baltimore, MD.

   Stem cells give rise to diverse cell types through cell differentiation. Differentiation programs are associated with a gradual reduction in cellular potency, accompanied by a corresponding stabilization in epigenetic plasticity potential. However, the chromatin-based mechanism underlying this differentiation-related reduction in epigenetic plasticity potential remains elusive. Here we report a new set of genes that play key roles in regulating epigenetic plasticity during ovarian follicle cell differentiation. With the capability of tracing epigenetic inheritance in vivo using the GAL4/UAS-GFP system, we performed systematic haploid deficiency screening at the second and the third chromosome to search for potential modifiers. As a result, we identified eight specific genes that dominantly modify the stabilization process of epigenetic plasticity, manifested as suppressed GFP variegation patterns as well as altered follicle cell differentiation. Interestingly, two of the most heavily represented classes of genes among the identified modifiers are cell cycle and epigenetic regulators. Together, our findings provide novel mechanistic insights on the molecular nature of epigenetic plasticity stabilization that underlies follicle cell differentiation.