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The PIWI protein MIWI2 and its associated PIWI-interacting RNAs (piRNAs) instruct DNA methylation of young active transposable elements (TEs) in the male germline. piRNAs are proposed to recruit MIWI2 to the transcriptionally active TE loci by base pairing to nascent transcripts, however the downstream mechanisms and effector proteins utilized by MIWI2 in directing de novo TE methylation remain incompletely understood. Here, we show that MIWI2 associates with TEX15 in foetal gonocytes. TEX15 is predominantly a nuclear protein that is not required for piRNA biogenesis but is essential for piRNA-directed TE de novo methylation and silencing. In summary, TEX15 is an essential executor of mammalian piRNA-directed DNA methylation.

Original publication

DOI

10.1038/s41467-020-17372-5

Type

Journal article

Journal

Nat Commun

Publication Date

27/07/2020

Volume

11

Keywords

Animals, Argonaute Proteins, Cell Cycle Proteins, DNA Methylation, DNA Transposable Elements, Female, Fetus, Gene Silencing, Genome, Germ Cells, Male, Mice, Mice, Inbred C57BL, Protein Binding, Testis