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Nature 451, 153-158 (10 January 2008) | doi:10.1038/nature06452; Received 3 August 2007; Accepted 5 November 2007; Published online 28 November 2007

RNA-mediated epigenetic programming of a genome-rearrangement pathway

Mariusz Nowacki1, Vikram Vijayan2, Yi Zhou1, Klaas Schotanus1, Thomas G. Doak1 & Laura F. Landweber1

  1. Department of Ecology and Evolutionary Biology, Princeton University, Princeton, New Jersey 08544, USA
  2. Department of Electrical Engineering, Princeton University, Princeton, New Jersey 08544, USA

Correspondence to: Laura F. Landweber1 Correspondence and requests for materials should be addressed to L.F.L. (Email: lfl@princeton.edu).

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Genome-wide DNA rearrangements occur in many eukaryotes but are most exaggerated in ciliates, making them ideal model systems for epigenetic phenomena. During development of the somatic macronucleus, Oxytricha trifallax destroys 95% of its germ line, severely fragmenting its chromosomes, and then unscrambles hundreds of thousands of remaining fragments by permutation or inversion. Here we demonstrate that DNA or RNA templates can orchestrate these genome rearrangements in Oxytricha, supporting an epigenetic model for sequence-dependent comparison between germline and somatic genomes. A complete RNA cache of the maternal somatic genome may be available at a specific stage during development to provide a template for correct and precise DNA rearrangement. We show the existence of maternal RNA templates that could guide DNA assembly, and that disruption of specific RNA molecules disables rearrangement of the corresponding gene. Injection of artificial templates reprogrammes the DNA rearrangement pathway, suggesting that RNA molecules guide genome rearrangement.

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