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

Aravin, A. A., Sachidanandam, R., Bourc'his, D., Schaefer, C., Pezic, D., Toth, K. F., Bestor, T., Hannon, G. 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 10972765 (ISSN)

URL: http://www.ncbi.nlm.nih.gov/pubmed/18922463
DOI: 10.1016/j.molcel.2008.09.003

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. © 2008 Elsevier Inc. All rights reserved.

Item Type: Paper
Uncontrolled Keywords: DNA PROTEINS RNA article cluster analysis cytoplasm DNA methylation Drosophila embryo embryo development female germ cell male mammal mouse nonhuman nuclear localization signal nucleotide sequence protein expression protein family transposon Animals Base Sequence DNA Transposable Elements Drosophila melanogaster Embryonic Development Genome Germ Cells Long Interspersed Nucleotide Elements Mice Models, Genetic Molecular Sequence Data Protein Binding RNA, Small Interfering Short Interspersed Nucleotide Elements Mammalia Mus
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > DNA methylation
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification
bioinformatics > genomics and proteomics > genetics & nucleic acid processing
organism description > animal > mammal > rodent > mouse
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > piRNA
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > transposons
CSHL Authors:
Communities: CSHL labs > Hannon lab
Depositing User: Matt Covey
Date Deposited: 09 Jan 2013 16:53
Last Modified: 09 Jan 2013 16:53
PMCID: PMC2730041
Related URLs:
URI: http://repository.cshl.edu/id/eprint/26450

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