A piRNA Pathway Primed by Individual Transposons Is Linked to De Novo DNA Methylation in Mice
26/09/2008
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.
Molecular Cell, Vol 31, 785-799, 26 September 2008
Molecular Cell, Vol 31, 785-799, 26 September 2008
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