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PMID:18381894

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Citation

Kuramochi-Miyagawa, S, Watanabe, T, Gotoh, K, Totoki, Y, Toyoda, A, Ikawa, M, Asada, N, Kojima, K, Yamaguchi, Y, Ijiri, TW, Hata, K, Li, E, Matsuda, Y, Kimura, T, Okabe, M, Sakaki, Y, Sasaki, H and Nakano, T (2008) DNA methylation of retrotransposon genes is regulated by Piwi family members MILI and MIWI2 in murine fetal testes. Genes Dev. 22:908-17

Abstract

Silencing of transposable elements occurs during fetal gametogenesis in males via de novo DNA methylation of their regulatory regions. The loss of MILI (miwi-like) and MIWI2 (mouse piwi 2), two mouse homologs of Drosophila Piwi, activates retrotransposon gene expression by impairing DNA methylation in the regulatory regions of the retrotransposons. However, as it is unclear whether the defective DNA methylation in the mutants is due to the impairment of de novo DNA methylation, we analyze DNA methylation and Piwi-interacting small RNA (piRNA) expression in wild-type, MILI-null, and MIWI2-null male fetal germ cells. We reveal that defective DNA methylation of the regulatory regions of the Line-1 (long interspersed nuclear elements) and IAP (intracisternal A particle) retrotransposons in the MILI-null and MIWI2-null male germ cells takes place at the level of de novo methylation. Comprehensive analysis shows that the piRNAs of fetal germ cells are distinct from those previously identified in neonatal and adult germ cells. The expression of piRNAs is reduced under MILI- and MIWI2-null conditions in fetal germ cells, although the extent of the reduction differs significantly between the two mutants. Our data strongly suggest that MILI and MIWI2 play essential roles in establishing de novo DNA methylation of retrotransposons in fetal male germ cells.

Links

PubMed PMC2279202 Online version:10.1101/gad.1640708

Keywords

Animals; Argonaute Proteins; Blotting, Northern; Cluster Analysis; CpG Islands/genetics; DNA Methylation; Female; Gene Expression Profiling; Gene Expression Regulation, Developmental; Genotype; Immunoprecipitation; Male; Mice; Mice, Knockout; Oligonucleotide Array Sequence Analysis; Protein Binding; Proteins/genetics; Proteins/metabolism; RNA, Untranslated/genetics; Retroelements/genetics; Reverse Transcriptase Polymerase Chain Reaction; Testis/cytology; Testis/embryology; Testis/metabolism

Significance

Annotations

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

MOUSE:PIWL4

involved_in

GO:0007283: spermatogenesis

ECO:0000315: mutant phenotype evidence used in manual assertion

P

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

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:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:PIWL2

involved_in

GO:0007283: spermatogenesis

ECO:0000315: mutant phenotype 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:0000315: mutant phenotype 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


See also

References

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