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PMID:18922463

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Citation

Aravin, AA, Sachidanandam, R, Bourc'his, D, Schaefer, C, Pezic, D, Toth, KF, Bestor, T and Hannon, GJ (2008) A piRNA pathway primed by individual transposons is linked to de novo DNA methylation in mice. Mol. Cell 31:785-99

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.

Links

PubMed PMC2730041 Online version:10.1016/j.molcel.2008.09.003

Keywords

Animals; Argonaute Proteins; Base Sequence; DNA Methylation; DNA Transposable Elements/genetics; Drosophila melanogaster/genetics; Embryonic Development; Genome/genetics; Germ Cells/metabolism; Long Interspersed Nucleotide Elements/genetics; Mice; Models, Genetic; Molecular Sequence Data; Protein Binding; Proteins/metabolism; RNA, Small Interfering/metabolism; Short Interspersed Nucleotide Elements/genetics

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:PIWL2

located_in

GO:0043186: P granule

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:PIWL4

enables

GO:0034584: piRNA binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:PIWL4

located_in

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:PIWL4

located_in

GO:0005737: cytoplasm

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:PIWL4

involved_in

GO:0031047: gene silencing by RNA

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:PIWL4

located_in

GO:0043186: P granule

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:PIWL4

involved_in

GO:0043046: DNA methylation involved in gamete generation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:PIWL4

involved_in

GO:0034587: piRNA metabolic process

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:PIWL2

involved_in

GO:0031047: gene silencing by RNA

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:PIWL2

enables

GO:0034584: piRNA binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:PIWL2

involved_in

GO:0034587: piRNA metabolic process

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:PIWL2

involved_in

GO:0043046: DNA methylation involved in gamete generation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:PIWL2

part_of

GO:0043186: P granule

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete


See also

References

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