Transcriptional states of retroelement-inserted regions and specific KRAB zinc finger protein association are correlated with DNA methylation of retroelements in human male germ cells
- RIKEN, Japan
- The University of Tokyo, Japan
- Tokyo Dental College Ichikawa General Hospital, Japan
- Nagoya University, Japan
Abstract
DNA methylation, repressive histone modifications, and PIWI-interacting RNAs are essential for controlling retroelement silencing in mammalian germ lines. Dysregulation of retroelement silencing is associated with male sterility. Although retroelement silencing mechanisms have been extensively studied in mouse germ cells, little progress has been made in humans. Here, we show that the Krüppel-associated box domain zinc finger proteins (KRAB-ZFPs) are associated with DNA methylation of retroelements in human primordial germ cells (hPGCs). Further, we show that the hominoid-specific retroelement SINE-VNTR-Alus (SVA) is subjected to transcription-directed de novo DNA methylation during human spermatogenesis. The degree of de novo DNA methylation in SVAs varies among human individuals, which confers significant inter-individual epigenetic variation in sperm. Collectively, our results highlight potential molecular mechanisms for the regulation of retroelements in human male germ cells.
Data availability
All reads from amplicon-seq in this study have been submitted to the Gene Expression Omnibus under accession number GSE174562.
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Amplicon-seq of SVA methylation in human spermNCBI Gene Expression Omnibus, GSE174562.
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ChIP-exo of human KRAB-ZNFs transduced in HEK 293T cells and KAP1 in hES H1 cellsNCBI Gene Expression OmnibusGSE78099.
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The Transcriptome and DNA Methylome Landscapes of Human Primordial Germ CellsNCBI Gene Expression OmnibusGSE63818.
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Genome-Wide Analysis of DNA Methylation Dynamics during Early Human Developmentthe Japanese Genotype-phenotype Archive, JGAS00000000006.
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Neonatal and adult human testis defined at the single-cell levelNCBI Gene Expression Omnibus,GSE124263.
Article and author information
Author details
Funding
Japan Society for the Promotion of Science (18H05530,18H03991)
- Yoichi Shinkai
RIKEN (SPDR)
- Kei Fukuda
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Deborah Bourc'his, Institut Curie, France
Ethics
Human subjects: This study was approved by the ethics committees of RIKEN, Tokyo University, and Ichikawa General Hospital.All study participants were briefed about the aims of the study and the parameters to be measured, and consent was obtained.
Version history
- Preprint posted: May 19, 2021 (view preprint)
- Received: January 6, 2022
- Accepted: March 21, 2022
- Accepted Manuscript published: March 22, 2022 (version 1)
- Version of Record published: March 30, 2022 (version 2)
Copyright
© 2022, Fukuda et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Transcriptional states of retroelement-inserted regions and specific KRAB zinc finger protein association are correlated with DNA methylation of retroelements in human male germ cells
eLife 11:e76822.
https://doi.org/10.7554/eLife.76822
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