Article

Piwi induces piRNA-guided transcriptional silencing and establishment of a repressive chromatin state

California Institute of Technology, Pasadena, California 91125, USA
Genes & development (Impact Factor: 10.8). 02/2013; 27(4). DOI: 10.1101/gad.209841.112
Source: PubMed

ABSTRACT

In the metazoan germline, piwi proteins and associated piwi-interacting RNAs (piRNAs) provide a defense system against the expression of transposable elements. In the cytoplasm, piRNA sequences guide piwi complexes to destroy complementary transposon transcripts by endonucleolytic cleavage. However, some piwi family members are nuclear, raising the possibility of alternative pathways for piRNA-mediated regulation of gene expression. We found that Drosophila Piwi is recruited to chromatin, colocalizing with RNA polymerase II (Pol II) on polytene chromosomes. Knockdown of Piwi in the germline increases expression of transposable elements that are targeted by piRNAs, whereas protein-coding genes remain largely unaffected. Derepression of transposons upon Piwi depletion correlates with increased occupancy of Pol II on their promoters. Expression of piRNAs that target a reporter construct results in a decrease in Pol II occupancy and an increase in repressive H3K9me3 marks and heterochromatin protein 1 (HP1) on the reporter locus. Our results indicate that Piwi identifies targets complementary to the associated piRNA and induces transcriptional repression by establishing a repressive chromatin state when correct targets are found.

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Available from: Adrien Le Thomas, Mar 06, 2014
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    • "This enhanced L1 insertion has also been demonstrated in vitro in a variety of cancer cell lines, which additionally display increased RNA polymerase II binding to TEs compared to non-malignant cell lines[49]. The PIWI protein localizes to the nucleus and works at the transcriptional level, establishing a repressive chromatin state as the result of an increase in H3K9me3 and HP1 chromatin marks (Fig. 2b)[41]. Overexpression of piRNA has been associated with the recruitment of PIWI, HP1a, and Su(var)3–9, the reduction of RNAPII,) includes: microRNAs (miRNAs), tRNA-derived fragment (tRF), PIWI-interacting RNAs (piRNAs), C/D snoRNA-derived RNA (sdRNAs), and small interfering RNAs (siRNAs). "
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    • "During PTGS, piRNAs guide Aubergine (Aub) and Argonaute 3 (Ago3) to TE transcripts, hence inducing their cleavage through Aub/Ago3 slicing activity (Brennecke et al, 2007; Li et al, 2009; Malone et al, 2009). During TGS, piRNAs guide Piwi to genomic TE copies, likely through nascent transcript recognition, where it promotes heterochromatinization through the deposition of repressive H3K9 methylation marks (Sienski et al, 2012; Darricarrere et al, 2013; Huang et al, 2013; Le Thomas et al, 2013; Rozhkov et al, 2013). In the absence of piRNAs, TEs become expressed and induce various oogenesis defects (early arrest of egg chamber development, dorsoventral patterning defects, etc.) leading to sterility. "
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    • "Piwi itself localizes to the nucleus and is involved in transcriptional repression through installation of the repressive H3K9me3 chromatin mark on target loci (Le Thomas et al., 2013; Rozhkov et al., 2013; Shpiz et al., 2011; Sienski et al., 2012). In contrast to Piwi, both Aub and Ago3 are cytoplasmic and endonucleolytically cleave transcripts complementary to their piRNA guide (Brennecke et al., 2007; Gunawardane et al., 2007; Huang et al., 2014). "
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