Chromatin: Probing a Pirna Paradox

RESEARCH HIGHLIGHTS

Nature Reviews Genetics | Published online 11 Sep 2017; doi:10.1038/nrg.2017.76

CHROMATIN bahri altay/iStockphoto/Thinkstock/Getty Probing a piRNA paradox

As a common mechanism to protect transcription was supported by its genome stability, transcription of enrichment at piRNA clusters, its repetitive DNA (such as transposons) interactions with other transcription typically results in processing into initiation proteins and, because its small RNAs to initiate sequence- knockout led to depleted piRNA specific heterochromatinization expression from the 42AB and of those elements genome-wide. 80F piRNA clusters, transposon However, a paradox then emerges as derepression and fly sterility. Based to how the resultant heterochromatin on this function, the authors named Furthermore, Rhino acts to divert (which is largely compacted and CG12721 ‘Moonshiner’ in reference transcripts into piRNA processing transcriptionally repressed) can still to its activity in the face of the pathways rather than mRNA matu- transcription serve as a source of small RNAs to transcriptional ‘prohibition’ of ration, thus minimizing the potential is triggered maintain the heterochromatic state. the heterochromatin environment. genome instability threat of generat- by a hetero A new study in Drosophila melano- Further investigations revealed ing full-length transposon transcripts gaster shows how heterochromatin a more complete mechanistic from piRNA clusters. chromatic histone marks can recruit specialized understanding of Moonshiner- It will be interesting to determine histone mark transcription machinery to generate mediated transcription at piRNA how evolutionarily pervasive it is PIWI-interacting RNAs (piRNAs). clusters. Compared with TFIIA-L, to specify small-RNA source loci Andersen et al. sought to under- Moonshiner lacks the carboxy- through chromatin marks rather than stand how piRNA cluster loci in terminal domain that would allow DNA sequence motifs. Andersen D. melanogaster are bidirectionally it to be recruited to promoters et al. note that although Rhino is not transcribed despite lacking overt bound by TATA-box binding conserved beyond fruit flies, SHH1 promoter DNA sequences and being protein (TBP). Instead, the authors has a similar role in plants by binding in heterochromatin that harbours the characterized a physical interaction to methylated H3K9 to recruit RNA classic repressive mark histone H3 between Moonshiner and the polymerase IV for the transcription lysine trimethylation (H3K9me3). Rhino–Deadlock complex as a of small-RNA precursors in the Deleting promoters in DNA flanking mechanism to recruit Moonshiner to RNA-directed DNA methylation the 42AB and 80F piRNA clusters piRNA cluster loci. Using a variety of (RdDM) pathway. As further indicated that these piRNA clusters genetic manipulations and tethering support that this principle may be were not transcribed via readthrough experiments the investigators showed widespread, a recent separate study from flanking regions. Instead, cap that Moonshiner can then recruit the by Jih et al. demonstrated that in the sequencing (Cap-seq) to pinpoint the TBP homologue TRF2 to form an fission yeast Schizosaccharomyces 5ʹ end of transcripts revealed perva- alternative TFIIA–TRF2 complex to pombe the subdomains of hetero- sive initiation of transcription from drive piRNA transcription. chromatin marked by H3K9me2 many sites within the piRNA clusters. The identification of Rhino- (rather than H3K9me3) are sources To identify potential molecular mediated Moonshiner recruitment of small RNAs for heterochromatin mediators of this transcription helps to explain the apparent paradox formation. initiation within piRNA clusters, the of how heterochromatin can be tran- Darren J. Burgess authors mined data from a published scribed to produce piRNAs. Rhino is transposon derepression screen, a heterochromatin protein 1 (HP1) ORIGINAL ARTICLES Andersen, P. R. et al. A heterochromatin-dependent transcription focusing on hits that have sequence paralogue that binds to H3K9me3, machinery drives piRNA expression. Nature http:// similarity to known transcription hence transcription is triggered by dx.doi.org/10.1038/nature23482 (2017) | Jih, G. initiation machinery. They identified a heterochromatic histone mark, et al. Unique roles for histone H3K9me states in RNAi and heritable silencing of transcription. CG12721 as a potential ovary-specific rather than requiring DNA-binding Nature 547, 463–467 (2017) paralogue of the large subunit of transcription factors to bind to their FURTHER READING Holoch, D. & Moazed, D. RNA-mediated epigenetic regulation of gene transcription factor IIA (TFIIA-L). inaccessible DNA target motifs expression. Nat. Rev. Genet. 16, 71–84 (2015) Its role as a driver of piRNA cluster in compacted heterochromatin.