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Originally published as Genetics Published Articles Ahead of Print on August 30, 2008.
Genetics, Vol. 180, 1275-1288, November 2008, Copyright © 2008
doi:10.1534/genetics.108.089433
Transmission Dynamics of Heritable Silencing Induced by Double-Stranded RNA in Caenorhabditis elegans
Rosa M. Alcazar*,
,
Rueyling Lin
and
Andrew Z. Fire*,,1
* Department of Pathology and Department of Genetics, Stanford University School of Medicine, Stanford, California 94305, Department of Biology, Johns Hopkins University and Carnegie Institution of Washington, Baltimore, Maryland 21218 and Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390
1 Corresponding author: Department of Pathology and Department of Genetics, Stanford University School of Medicine, 300 Pasteur Dr., Room L235, Stanford, CA 94305-5324.
E-mail: afire{at}stanford.edu
Heritable silencing effects are gene suppression phenomena that can persist for generations after induction. In the majority of RNAi experiments conducted in Caenorhabditis elegans, the silencing response results in a hypomorphic phenotype where the effects recede after the F1 generation. F2 and subsequent generations revert to the original phenotype. Specific examples of transgenerational RNAi in which effects persist to the F2 generation and beyond have been described. In this study, we describe a systematic pedigree-based analysis of heritable silencing processes resulting from initiation of interference targeted at the C. elegans oocyte maturation factor oma-1. Heritable silencing of oma-1 is a dose-dependent process where the inheritance of the silencing factor is unequally distributed among the population. Heritability is not constant over generational time, with silenced populations appearing to undergo a bottleneck three to four generations following microinjection of RNA. Transmission of silencing through these generations can be through either maternal or paternal gamete lines and is surprisingly more effective through the male gametic line. Genetic linkage tests reveal that silencing in the early generations is transmitted independently of the original targeted locus, in a manner indicative of a diffusible epigenetic element.
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Genetics 2008 180: NP.