SPOCD1 is an essential executor of piRNA-directed de novo DNA methylation

Ansgar Zoch, Tania Auchynnikava, Rebecca V. Berrens, Yuka Kabayama, Theresa Schöpp, Madeleine Heep, Lina Vasiliauskaitė, Yuvia A. Pérez-Rico, Atlanta G. Cook, Alena Shkumatava, Juri Rappsilber, Robin C. Allshire and Dónal O’Carroll ()
Additional contact information
Ansgar Zoch: University of Edinburgh
Tania Auchynnikava: University of Edinburgh
Rebecca V. Berrens: University of Cambridge, Li Ka Shing Centre
Yuka Kabayama: University of Edinburgh
Theresa Schöpp: University of Edinburgh
Madeleine Heep: University of Edinburgh
Lina Vasiliauskaitė: University of Edinburgh
Yuvia A. Pérez-Rico: PSL Research University, CNRS UMR 3215, INSERM U934
Atlanta G. Cook: University of Edinburgh
Alena Shkumatava: PSL Research University, CNRS UMR 3215, INSERM U934
Juri Rappsilber: University of Edinburgh
Robin C. Allshire: University of Edinburgh
Dónal O’Carroll: University of Edinburgh

Nature, 2020, vol. 584, issue 7822, 635-639

Abstract: Abstract In mammals, the acquisition of the germline from the soma provides the germline with an essential challenge: the need to erase and reset genomic methylation1. In the male germline, RNA-directed DNA methylation silences young, active transposable elements2–4. The PIWI protein MIWI2 (PIWIL4) and its associated PIWI-interacting RNAs (piRNAs) instruct DNA methylation of transposable elements3,5. piRNAs are proposed to tether MIWI2 to nascent transposable element transcripts; however, the mechanism by which MIWI2 directs the de novo methylation of transposable elements is poorly understood, although central to the immortality of the germline. Here we define the interactome of MIWI2 in mouse fetal gonocytes undergoing de novo genome methylation and identify a previously unknown MIWI2-associated factor, SPOCD1, that is essential for the methylation and silencing of young transposable elements. The loss of Spocd1 in mice results in male-specific infertility but does not affect either piRNA biogenesis or the localization of MIWI2 to the nucleus. SPOCD1 is a nuclear protein whose expression is restricted to the period of de novo genome methylation. It co-purifies in vivo with DNMT3L and DNMT3A, components of the de novo methylation machinery, as well as with constituents of the NURD and BAF chromatin remodelling complexes. We propose a model whereby tethering of MIWI2 to a nascent transposable element transcript recruits repressive chromatin remodelling activities and the de novo methylation apparatus through SPOCD1. In summary, we have identified a previously unrecognized and essential executor of mammalian piRNA-directed DNA methylation.

Date: 2020
References: Add references at CitEc
Citations: View citations in EconPapers (4)

Downloads: (external link)
https://www.nature.com/articles/s41586-020-2557-5 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:584:y:2020:i:7822:d:10.1038_s41586-020-2557-5

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/s41586-020-2557-5

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().