title: Stable Heritable Germline Silencing Directs Somatic Silencing at an Endogenous Locus.
abstract: The importance of transgenerationally inherited epigenetic states to organismal fitness remains unknown as well-documented examples are often not amenable to mechanistic analysis or rely on artificial reporter loci. Here we describe an induced silenced state at an endogenous locus that persists, at 100% transmission without selection, for up to 13 generations. This unusually persistent silencing enables a detailed molecular genetic analysis of an inherited epigenetic state. We find that silencing is dependent on germline nuclear RNAi factors and post-transcriptional mechanisms. Consistent with these later observations, inheritance does not require the silenced locus, and we provide genetic evidence that small RNAs embody the inherited silencing signal. Notably, heritable germline silencing directs somatic epigenetic silencing. Somatic silencing does not require somatic nuclear RNAi but instead requires both maternal germline nuclear RNAi and chromatin-modifying activity. Coupling inherited germline silencing to somatic silencing may enable selection for physiologically important traits.
authors.affiliation: Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA.
authors.forename: Olga
authors.initials: O
authors.lastname: Minkina
authors.affiliation: Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA. Electronic address: cphunter@g.harvard.edu.
authors.forename: Craig P
authors.initials: CP
authors.lastname: Hunter
mesh_terms: D020121:5' Untranslated Regions; D000818:Animals; D030801:Animals, Genetically Modified; D060565:Argonaute Proteins / Q000235:genetics / Q000378:metabolism; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000378:metabolism; D002843:Chromatin / Q000235:genetics / Q000378:metabolism; D042002:Chromatin Assembly and Disassembly; D020868:Gene Silencing; D056426:Genetic Loci; D005838:Genotype; D040941:Heredity; D040582:Inheritance Patterns; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D010641:Phenotype; D011401:Promoter Regions, Genetic; D034622:RNA Interference; D012322:RNA Precursors / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics* / Q000378:metabolism
chemical_list: D020121:5' Untranslated Regions; D060565:Argonaute Proteins; D029742:Caenorhabditis elegans Proteins; D002843:Chromatin; C576015:HRDE-1 protein, C elegans; D008565:Membrane Proteins; D009687:Nuclear Proteins; C530363:PRG-1 protein, C elegans; D012322:RNA Precursors; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C452203:SID-1 protein, C elegans
keywords: C. elegans; epigenetics; nuclear RNAi; piRNAs; sid-1; transgenerational inheritance