A piRNA Pathway Primed by Individual Transposons Is Linked to De Novo DNA Methylation in Mice
Abstract
piRNAs and Piwi proteins have been implicated in transposon control and are linked to transposon methylation in mammals. Here we examined the construction of the piRNA system in the restricted developmental window in which methylation patterns are set during mammalian embryogenesis. We find robust expression of two Piwi family proteins, MIWI2 and MILI. Their associated piRNA profiles reveal differences from Drosophila wherein large piRNA clusters act as master regulators of silencing. Instead, in mammals, dispersed transposon copies initiate the pathway, producing primary piRNAs, which predominantly join MILI in the cytoplasm. MIWI2, whose nuclear localization and association with piRNAs depend upon MILI, is enriched for secondary piRNAs antisense to the elements that it controls. The Piwi pathway lies upstream of known mediators of DNA methylation, since piRNAs are still produced in dnmt3L mutants, which fail to methylate transposons. This implicates piRNAs as specificity determinants of DNA methylation in germ cells.
Additional Information
© 2008 Elsevier Inc. Received 2 June 2008, Revised 5 September 2008, Accepted 10 September 2008, Available online 25 September 2008. We thank Sang Yong Kim (Cold Spring Harbor Laboratory, CSHL) for generating transgenic animals. We thank Maria Mosquera, Lisa Bianco, Jodi Coblentz, and Gula Nourjanova (CSHL) for animal assistance and histology. We thank Stephen Hearn (CSHL) for microscopy assistance and Emily Hodges, Michelle Rooks, Dick Mccombie, Danea Rebolini, and Laura Cardone for help with Illumina sequencing. We thank Catherine Schlingheyde for help with experiments and members of the Hannon laboratory, especially Antoine Molaro, for comments on the manuscript. G.J.H. is an investigator of the Howard Hughes Medical Institute. This work was supported by grants from the National Institutes of Health (NIH) to G.J.H. and an NIH Pathway to Independence Award K99HD057233 to A.A.A. Accession Numbers: Sequences reported in this manuscript are available in the Gene Expression Omnibus under accession number GSE12757.Attached Files
Accepted Version - nihms72596.pdf
Supplemental Material - 1-s2.0-S1097276508006199-mmc1.pdf
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Additional details
- PMCID
- PMC2730041
- Eprint ID
- 95352
- Resolver ID
- CaltechAUTHORS:20190508-133919077
- Howard Hughes Medical Institute (HHMI)
- K99HD057233
- NIH
- Created
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2019-05-09Created from EPrint's datestamp field
- Updated
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2021-11-16Created from EPrint's last_modified field