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

Nature
Ansgar ZochDónal O'Carroll

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 machi...Continue Reading

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Citations

Jul 29, 2020·Nature Communications·Theresa SchöppDónal O'Carroll
Sep 9, 2020·Signal Transduction and Targeted Therapy·Zhiqing LiEn-Zhi Shen
Aug 14, 2020·Nature Structural & Molecular Biology·Maria Ninova, Katalin Fejes Tóth
Nov 28, 2020·Biochemical Society Transactions·Stephen K WuAaron M Johnson
Nov 18, 2020·Proceedings of the National Academy of Sciences of the United States of America·Masayuki TsuzukiAndrzej T Wierzbicki
Mar 7, 2021·International Journal of Molecular Sciences·Kayla J RayfordPius N Nde
May 12, 2021·Genome Biology·Natasha Jansz, Geoffrey J Faulkner
May 28, 2021·Frontiers in Cell and Developmental Biology·Anirudh PillaiSanjeev Galande
May 30, 2021·Development, Growth & Differentiation·Hitoshi Ohtani, Yuka W Iwasaki
Jun 14, 2021·Journal of Hematology & Oncology·Silu ChenMeilin Wang
Aug 3, 2021·Frontiers in Cell and Developmental Biology·Yinuo LiMingxi Liu
Jun 24, 2021·Biology of Reproduction·Sean M CullenMatthew Smith-Raska
Nov 12, 2021·PeerJ·Javier GutierrezMichael Vandewege

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Datasets Mentioned

BETA
E-MTAB-5056
SRP037785
GSE84140

Methods Mentioned

BETA
immunoprecipitation
RNA-seq
methylation sequencing
immunoprecipitations
PCR
fluorescence-activated cell sorting
FACS
Methyl-seq
transfection

Software Mentioned

RepeatMasker
R Studio
ClustalW
PHYRE2
Clustal Omega
Metaplot
cNLS mapper
COFFEE
R
Airyscan

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