Small RNA-Directed Silencing: The Fly Finds Its Inner Fission Yeast?
ABSTRACT Several recent studies demonstrate that piRNAs guide Piwi protein to repress transposon transcription in fly ovaries, much as fission yeast use siRNAs to silence repeat sequences. Still mysterious though is how Piwi targets euchromatic transposons for silencing, but not the specialized heterochromatic loci that produce piRNA precursors.
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ABSTRACT: In the ciliate Paramecium tetraurelia, differentiation of the somatic nucleus from the zygotic nucleus is characterized by massive and reproducible deletion of transposable elements and of 45,000 short, dispersed, single-copy sequences. A specific class of small RNAs produced by the germline during meiosis, the scnRNAs, are involved in the epigenetic regulation of DNA deletion but the underlying mechanisms are poorly understood. Here, we show that trimethylation of histone H3 (H3K27me3 and H3K9me3) displays a dynamic nuclear localization that is altered when the endonuclease required for DNA elimination is depleted. We identified the putative histone methyltransferase Ezl1 necessary for H3K27me3 and H3K9me3 establishment and show that it is required for correct genome rearrangements. Genome-wide analyses show that scnRNA-mediated H3 trimethylation is necessary for the elimination of long, repeated germline DNA, while single copy sequences display differential sensitivity to depletion of proteins involved in the scnRNA pathway, Ezl1- a putative histone methyltransferase and Dcl5- a protein required for iesRNA biogenesis. Our study reveals cis-acting determinants, such as DNA length, also contribute to the definition of germline sequences to delete. We further show that precise excision of single copy DNA elements, as short as 26 bp, requires Ezl1, suggesting that development specific H3K27me3 and H3K9me3 ensure specific demarcation of very short germline sequences from the adjacent somatic sequences.PLoS Genetics 09/2014; 10(9):e1004665. DOI:10.1371/journal.pgen.1004665 · 8.17 Impact Factor
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ABSTRACT: The Piwi-interacting RNA (piRNA)-interacting Piwi protein is involved in transcriptional silencing of transposable elements in ovaries of Drosophila melanogaster. Here we characterized the genome-wide effect of nuclear Piwi elimination on the presence of the heterochromatic H3K9me3 mark and HP1a, as well as on the transcription-associated mark H3K4me2. Our results demonstrate that a significant increase in the H3K4me2 level upon nuclear Piwi loss is not accompanied by the alterations in H3K9me3 and HP1a levels for several germline-expressed transposons, suggesting that in this case Piwi prevents transcription by a mechanism distinct from H3K9 methylation. We found that the targets of Piwi-dependent chromatin repression are mainly related to the elements that display a higher level of H3K4me2 modification in the absence of silencing, i.e. most actively transcribed elements. We also show that Piwi-guided silencing does not significantly influence the chromatin state of dual-strand piRNA-producing clusters. In addition, host protein-coding gene expression is essentially not affected due to the nuclear Piwi elimination, but we noted an increase in small nuclear spliceosomal RNAs abundance and propose Piwi involvement in their post-transcriptional regulation. Our work reveals new aspects of transposon silencing in Drosophila, indicating that transcription of transposons can underpin their Piwi dependent silencing, while canonical heterochromatin marks are not obligatory for their repression.Nucleic Acids Research 04/2014; 42(10). DOI:10.1093/nar/gku268 · 8.81 Impact Factor
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ABSTRACT: The discovery of millions of PIWI-interacting RNAs revealed a fascinating and unanticipated dimension of biology. The PIWI-piRNA pathway has been commonly perceived as germline-specific, even though the somatic function of PIWI proteins was documented when they were first discovered. Recent studies have begun to re-explore this pathway in somatic cells in diverse organisms, particularly lower eukaryotes. These studies have illustrated the multifaceted somatic functions of the pathway not only in transposon silencing but also in genome rearrangement and epigenetic programming, with biological roles in stem-cell function, whole-body regeneration, memory and possibly cancer.Nature 01/2014; 505(7483):353-9. DOI:10.1038/nature12987 · 42.35 Impact Factor