Environmentally induced rDNA instability as a driver of epigenetic variation. John Aldrich, Keith Maggert. Department of Biology, Texas A&M University, College Station, TX.

   An organisms patterns of gene expression are responsive to environmental input. Often, this influence is not limited to short-term regulatory changes, but can persist through multiple cell divisions and can, in some cases, be transmitted to offspring. It is typically assumed that such epigenetic changes are mediated by chromatin modifications in the form of histone or DNA modifications or expression of regulatory RNAs. However, the mechanisms through which epigenetic changes are established at specific promoters, are maintained through mitoses and meioses, and affect an organism's phenotypes remain unclear. In this work, we show that alterations to diet affect the expression of the ribosomal RNA genes which in turn results in DNA damage and loss of rDNA. These induced genomic changes have all the hallmarks of epigenetics since they are inducible, heritable, and consequential. We show that mutations in silencing factors result in nucleolar fragmentation and rDNA copy number reduction. Furthermore, we find that drugs that alter rDNA expression suppress these effects. This induced variation is stable throughout development, and correlates with altered heterochromatic silencing and gene expression. Dietary perturbation in adults alters the rDNA of offspring, providing a clear mechanism for transgenerational inheritance of dietary effects in flies.