PNAS-2010-RNA-mediated epigenetic regulation of DNA copy number.pdf

RNA-mediated epigenetic regulation of DNA copy number Mariusz Nowackia,b,1, Joanna E. Hayea, Wenwen Fanga, Vikram Vijayana,c, and Laura F. Landwebera,1 aDepartment of Ecology and Evolutionary Biology, Princeton University, Princeton, NJ 08544; bInstitute of Cell Biology, University of Bern, 3012 Bern, Switzerland; and cDepartment of Systems Biology, Harvard Medical School, Boston, MA 02115 Edited* by Mark T. Groudine, The Fred Hutchinson Cancer Research Center, Seattle, WA, and approved October 21, 2010 (received for review August 18, 2010) Increasing evidence suggests that parentally supplied RNA plays crucial roles during eukaryotic development. This epigenetic con- tribution may regulate gene expression from the earliest stages. Although present in a variety of eukaryotes, maternally inherited characters are especially prominent in ciliated protozoa, in which parental noncoding RNA molecules instruct whole-genome re- organization. This includes removal of nearly all noncoding DNA and sorting the remaining fragments, producing extremely gene- rich somatic genomes. Chromosome fragmentation and extensive replication produce variable DNA copy numbers in the somatic genome. Understanding the forces that drive and regulate copy number change is fundamental. We show that RNA molecules present in parental cells during sexual reproduction can regulate chromosome copy number in the developing nucleus of the ciliate Oxytricha. Experimentally induced changes in RNA abundance can both increase and decrease the levels of corresponding DNA mole- cules in progeny, demonstrating epigenetic inheritance of chromo- some copy number. These results suggest that maternal RNA, in addition to controlling gene expression or DNAprocessing, can also program DNA amplification levels. copy number variation | genome rearrangement DNA copy number profoundly influences evolution (1–4),permitting changes in gene and protein expression (5–7) that may be acted upon by positive selection (7), permit