MORC1 represses transposable elements in the mouse male germline.

William A Pastor,Kevin Nee,Steven E Jacobsen,Hume Stroud,Serena A Lee,Natasha Zamudio,Dubravka Pezic,Wanlu Liu,Sergei Manakov,Guillaume Moissiard,Alexei A Aravin,Amander T Clark,Déborah Bourc’His

doi:10.1038/ncomms6795

Abstract

The Microrchidia (Morc) family of GHKL ATPases are present in a wide variety of prokaryotic and eukaryotic organisms but are of largely unknown function. Genetic screens in Arabidopsis thaliana have identified Morc genes as important repressors of transposons and other DNA-methylated and silent genes. MORC1-deficient mice were previously found to display male-specific germ cell loss and infertility. Here we show that MORC1 is responsible for transposon repression in the male germline in a pattern that is similar to that observed for germ cells deficient for the DNA methyltransferase homologue DNMT3L. Morc1 mutants show highly localized defects in the establishment of DNA methylation at specific classes of transposons, and this is associated with failed transposon silencing at these sites. Our results identify MORC1 as an important new regulator of the epigenetic landscape of male germ cells during the period of global de novo methylation.

Highlights

The Microrchidia (Morc) family of GHKL ATPases are present in a wide variety of prokaryotic and eukaryotic organisms but are of largely unknown function
Quantative reverse transcription-PCR from wild type (WT), embryonic whole testis indicates that Morc[1] messenger RNA becomes detectable at E14.5 and peaks at E16.5 (Supplementary Fig. 2a), which intriguingly is a period of rapid transposon methylation in the male germline
We generated an antibody against the coiled-coil domain of mouse MORC1 (Supplementary Fig. 2b) and found that MORC1 was localized to the nucleus of male germ cells at E16.5 (Fig. 1b)

Summary

Introduction

The Microrchidia (Morc) family of GHKL ATPases are present in a wide variety of prokaryotic and eukaryotic organisms but are of largely unknown function. Genetic screens in Arabidopsis thaliana have identified Morc genes as important repressors of transposons and other DNA-methylated and silent genes. We show that MORC1 is responsible for transposon repression in the male germline in a pattern that is similar to that observed for germ cells deficient for the DNA methyltransferase homologue DNMT3L. Morc[1] mutants show highly localized defects in the establishment of DNA methylation at specific classes of transposons, and this is associated with failed transposon silencing at these sites. Our results identify MORC1 as an important new regulator of the epigenetic landscape of male germ cells during the period of global de novo methylation. We demonstrate that MORC1-deficient male germ cells undergo transposon derepression starting in late embryogenesis and continuing through the onset of meiosis. We demonstrate that this phenotype is associated with failed locus-specific de novo methylation targeted towards late-methylating transposon sequences

Methods

Results

Conclusion