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A piRNA Pathway Primed by Individual Transposons Is Linked to De Novo DNA Methylation in Mice

Aravin, Alexei A. and Sachidanandam, Ravi and Bourc'his, Deborah and Schaefer, Christopher and Pezic, Dubravka and Fejes Toth, Katalin and Bestor, Timothy and Hannon, Gregory J. (2008) A piRNA Pathway Primed by Individual Transposons Is Linked to De Novo DNA Methylation in Mice. Molecular Cell, 31 (6). pp. 785-799. ISSN 1097-2765. PMCID PMC2730041. https://resolver.caltech.edu/CaltechAUTHORS:20190508-133919077

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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.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1016/j.molcel.2008.09.003DOIArticle
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2730041PubMed CentralArticle
ORCID:
AuthorORCID
Fejes Toth, Katalin0000-0001-6558-2636
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.
Funders:
Funding AgencyGrant Number
Howard Hughes Medical Institute (HHMI)UNSPECIFIED
NIHK99HD057233
Subject Keywords:DNA; RNA; Proteins
Issue or Number:6
PubMed Central ID:PMC2730041
Record Number:CaltechAUTHORS:20190508-133919077
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20190508-133919077
Official Citation:Alexei A. Aravin, Ravi Sachidanandam, Deborah Bourc'his, Christopher Schaefer, Dubravka Pezic, Katalin Fejes Toth, Timothy Bestor, Gregory J. Hannon, A piRNA Pathway Primed by Individual Transposons Is Linked to De Novo DNA Methylation in Mice, Molecular Cell, Volume 31, Issue 6, 2008, Pages 785-799, ISSN 1097-2765, https://doi.org/10.1016/j.molcel.2008.09.003. (http://www.sciencedirect.com/science/article/pii/S1097276508006199)
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:95352
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:09 May 2019 17:38
Last Modified:03 Oct 2019 21:12

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