RRC ID 59396
著者 Perales R, Pagano D, Wan G, Fields BD, Saltzman AL, Kennedy SG.
タイトル Transgenerational Epigenetic Inheritance Is Negatively Regulated by the HERI-1 Chromodomain Protein.
ジャーナル Genetics
Abstract Transgenerational epigenetic inheritance (TEI) is the inheritance of epigenetic information for two or more generations. In most cases, TEI is limited to a small number of generations (two to three). The short-term nature of TEI could be set by innate biochemical limitations to TEI or by genetically encoded systems that actively limit TEI. In Caenorhabditis elegans, double-stranded RNA (dsRNA)-mediated gene silencing [RNAi (RNA interference)] can be inherited (termed RNAi inheritance or RNA-directed TEI). To identify systems that might actively limit RNA-directed TEI, we conducted a forward genetic screen for factors whose mutation enhanced RNAi inheritance. This screen identified the gene heritable enhancer of RNAi (heri-1), whose mutation causes RNAi inheritance to last longer (> 20 generations) than normal. heri-1 encodes a protein with a chromodomain, and a kinase homology domain that is expressed in germ cells and localizes to nuclei. In C. elegans, a nuclear branch of the RNAi pathway [termed the nuclear RNAi or NRDE (nuclear RNA defective) pathway] promotes RNAi inheritance. We find that heri-1(-) animals have defects in spermatogenesis that are suppressible by mutations in the nuclear RNAi Argonaute (Ago) HRDE-1, suggesting that HERI-1 might normally act in sperm progenitor cells to limit nuclear RNAi and/or RNAi inheritance. Consistent with this idea, we find that the NRDE nuclear RNAi pathway is hyperresponsive to experimental RNAi treatments in heri-1 mutant animals. Interestingly, HERI-1 binds to genes targeted by RNAi, suggesting that HERI-1 may have a direct role in limiting nuclear RNAi and, therefore, RNAi inheritance. Finally, the recruitment of HERI-1 to chromatin depends upon the same factors that drive cotranscriptional gene silencing, suggesting that the generational perdurance of RNAi inheritance in C. elegans may be set by competing pro- and antisilencing outputs of the nuclear RNAi machinery.
巻・号 210(4)
ページ 1287-1299
公開日 2018-12-1
DOI 10.1534/genetics.118.301456
PII genetics.118.301456
PMID 30389807
PMC PMC6283161
MeSH Animals Argonaute Proteins / genetics* Caenorhabditis elegans / genetics Caenorhabditis elegans Proteins / genetics* Cell Nucleus / genetics Chromatin / genetics Enhancer Elements, Genetic / genetics* Epigenesis, Genetic Gene Silencing Inheritance Patterns / genetics Nuclear Proteins / genetics* Protein Kinases / genetics* RNA Interference* RNA, Double-Stranded / genetics
IF 3.564
引用数 4
リソース情報
線虫 tm1200