Relationship between PIWIL4-Mediated H3K4me2 Demethylation and piRNA-Dependent DNA Methylation

Ippei Nagamori; Hisato Kobayashi; Toru Nishimura; Reina Yamagishi; Jun Katahira; Satomi Kuramochi-Miyagawa; Tomohiro Kono; Toru Nakano

doi:10.1016/j.celrep.2018.09.017

Relationship between PIWIL4-Mediated H3K4me2 Demethylation and piRNA-Dependent DNA Methylation

Cell Rep. 2018 Oct 9;25(2):350-356. doi: 10.1016/j.celrep.2018.09.017.

Authors

Ippei Nagamori¹, Hisato Kobayashi², Toru Nishimura³, Reina Yamagishi³, Jun Katahira⁴, Satomi Kuramochi-Miyagawa⁵, Tomohiro Kono⁶, Toru Nakano⁷

Affiliations

¹ Department of Pathology, Medical School, Osaka University, Suita 565-0871, Osaka, Japan. Electronic address: inagamor@patho.med.osaka-u.ac.jp.
² NODAI Genome Research Center, Tokyo University of Agriculture, Setagaya-ku 156-8502, Tokyo, Japan.
³ Graduate School of Frontier Biosciences, Osaka University, Suita 565-0871, Osaka, Japan.
⁴ Department of Pathology, Medical School, Osaka University, Suita 565-0871, Osaka, Japan.
⁵ Department of Pathology, Medical School, Osaka University, Suita 565-0871, Osaka, Japan; Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency (JST), Saitama 332-0012, Japan.
⁶ Department of Bioscience, Tokyo University of Agriculture, Setagaya-ku 156-8502, Tokyo, Japan.
⁷ Department of Pathology, Medical School, Osaka University, Suita 565-0871, Osaka, Japan; Graduate School of Frontier Biosciences, Osaka University, Suita 565-0871, Osaka, Japan; Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency (JST), Saitama 332-0012, Japan. Electronic address: tnakano@patho.med.osaka-u.ac.jp.

PMID: 30304676
DOI: 10.1016/j.celrep.2018.09.017

Abstract

Retrotransposon genes are silenced by DNA methylation because of potential harm due to insertional mutagenesis. DNA methylation of retrotransposon genes is erased and re-established during male germ cell development. Both piRNA-dependent and piRNA-independent mechanisms are active during the re-establishment process, with the piRNA-independent mechanism occurring first. In this study, we analyzed the role of PIWIL4/MIWI2 in the modification of histone H3 and subsequent piRNA-dependent DNA methylation. Dimethylation at H3K4 is highly enriched at piRNA-dependent methylated regions and anti-correlated with de novo DNA methylation during the phase of piRNA-independent DNA methylation. In addition, PIWIL4, which binds the H3K4 demethylases KDM1A and KDM5B, is required for removing H3K4me2 marks. These data show that PIWIL4 plays important roles in histone modification and piRNA-dependent DNA methylation.

Keywords: DNA methylation; germ cell; gonocyte; piRNA; spermatogenesis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Argonaute Proteins / antagonists & inhibitors
Argonaute Proteins / genetics
Argonaute Proteins / metabolism*
Cells, Cultured
DNA Methylation*
DNA-Binding Proteins / genetics
DNA-Binding Proteins / metabolism*
Embryo, Mammalian / cytology
Embryo, Mammalian / metabolism*
Gene Expression Regulation, Developmental
Histone Demethylases / genetics
Histone Demethylases / metabolism*
Histones / chemistry*
Histones / genetics
Jumonji Domain-Containing Histone Demethylases / genetics
Jumonji Domain-Containing Histone Demethylases / metabolism*
Lysine / chemistry*
Lysine / genetics
Male
Mice
Mice, Transgenic
RNA, Small Interfering / genetics*

Substances

Argonaute Proteins
DNA-Binding Proteins
Histones
PIWIL4 protein, mouse
RNA, Small Interfering
Histone Demethylases
Jumonji Domain-Containing Histone Demethylases
KDM1a protein, mouse
Kdm5b protein, mouse
Lysine