title: Transgenerationally inherited piRNAs trigger piRNA biogenesis by changing the chromatin of piRNA clusters and inducing precursor processing.
abstract: Small noncoding RNAs that associate with Piwi proteins, called piRNAs, serve as guides for repression of diverse transposable elements in germ cells of metazoa. In Drosophila, the genomic regions that give rise to piRNAs, the so-called piRNA clusters, are transcribed to generate long precursor molecules that are processed into mature piRNAs. How genomic regions that give rise to piRNA precursor transcripts are differentiated from the rest of the genome and how these transcripts are specifically channeled into the piRNA biogenesis pathway are not known. We found that transgenerationally inherited piRNAs provide the critical trigger for piRNA production from homologous genomic regions in the next generation by two different mechanisms. First, inherited piRNAs enhance processing of homologous transcripts into mature piRNAs by initiating the ping-pong cycle in the cytoplasm. Second, inherited piRNAs induce installment of the histone 3 Lys9 trimethylation (H3K9me3) mark on genomic piRNA cluster sequences. The heterochromatin protein 1 (HP1) homolog Rhino binds to the H3K9me3 mark through its chromodomain and is enriched over piRNA clusters. Rhino recruits the piRNA biogenesis factor Cutoff to piRNA clusters and is required for efficient transcription of piRNA precursors. We propose that transgenerationally inherited piRNAs act as an epigenetic memory for identification of substrates for piRNA biogenesis on two levels: by inducing a permissive chromatin environment for piRNA precursor synthesis and by enhancing processing of these precursors.
authors.affiliation: Division of Biology, California Institute of Technology, Pasadena, California 91125, USA; Ecole Doctorale Complexité du Vivant, Université Pierre et Marie Curie, 75005 Paris, France;
authors.forename: Adrien
authors.initials: A
authors.lastname: Le Thomas
authors.affiliation: Division of Biology, California Institute of Technology, Pasadena, California 91125, USA; Biochemistry Center Regensburg, Laboratory for RNA Biology, University of Regensburg, 93053 Regensburg, Germany;
authors.forename: Evelyn
authors.initials: E
authors.lastname: Stuwe
authors.affiliation: Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA;
authors.forename: Sisi
authors.initials: S
authors.lastname: Li
authors.affiliation: Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA; aaa@caltech.edu.
authors.forename: Jiamu
authors.initials: J
authors.lastname: Du
authors.affiliation: Division of Biology, California Institute of Technology, Pasadena, California 91125, USA;
authors.forename: Georgi
authors.initials: G
authors.lastname: Marinov
authors.affiliation: Watson School of Biological Sciences, Howard Hughes Medical Institute, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA;
authors.forename: Nikolay
authors.initials: N
authors.lastname: Rozhkov
authors.affiliation: Division of Biology, California Institute of Technology, Pasadena, California 91125, USA;
authors.forename: Yung-Chia Ariel
authors.initials: YC
authors.lastname: Chen
authors.affiliation: Division of Biology, California Institute of Technology, Pasadena, California 91125, USA;
authors.forename: Yicheng
authors.initials: Y
authors.lastname: Luo
authors.affiliation: Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York, New York 10029, USA.
authors.forename: Ravi
authors.initials: R
authors.lastname: Sachidanandam
authors.affiliation: Division of Biology, California Institute of Technology, Pasadena, California 91125, USA;
authors.forename: Katalin Fejes
authors.initials: KF
authors.lastname: Toth
authors.affiliation: Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA;
authors.forename: Dinshaw
authors.initials: D
authors.lastname: Patel
authors.affiliation: Division of Biology, California Institute of Technology, Pasadena, California 91125, USA;
authors.forename: Alexei A
authors.initials: AA
authors.lastname: Aravin
mesh_terms: D000818:Animals; D002843:Chromatin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D019175:DNA Methylation; D004330:Drosophila / Q000235:genetics* / Q000378:metabolism*; D029721:Drosophila Proteins / Q000378:metabolism; D044127:Epigenesis, Genetic; D005786:Gene Expression Regulation; D006657:Histones / Q000378:metabolism; D005810:Multigene Family / Q000235:genetics; D011485:Protein Binding; D012322:RNA Precursors / Q000378:metabolism*; D058727:RNA, Small Untranslated / Q000096:biosynthesis* / Q000235:genetics*; D016601:RNA-Binding Proteins / Q000378:metabolism; D019076:Transgenes
chemical_list: D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; C000590395:Cuff protein, Drosophila; D029721:Drosophila Proteins; D006657:Histones; D012322:RNA Precursors; D058727:RNA, Small Untranslated; D016601:RNA-Binding Proteins; C449641:rhi protein, Drosophila
keywords: H3K9me3; epigenetics; piRNA
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