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

  1. Kei Fukuda  Is a corresponding author
  2. Yoshinori Makino
  3. Satoru Kaneko
  4. Chikako Shimura
  5. Yuki Okada
  6. Kenji Ichiyanagi
  7. Yoichi Shinkai  Is a corresponding author
  1. RIKEN, Japan
  2. The University of Tokyo, Japan
  3. Tokyo Dental College Ichikawa General Hospital, Japan
  4. 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.

The following data sets were generated
The following previously published data sets were used

Article and author information

Author details

  1. Kei Fukuda

    Cellular Memory Laboratory, RIKEN, Wako, Japan
    For correspondence
    kei.fukuda@riken.jp
    Competing interests
    The authors declare that no competing interests exist.
  2. Yoshinori Makino

    Institute for Quantitative Biosciences, The University of Tokyo, Tokyo, Japan
    Competing interests
    The authors declare that no competing interests exist.
  3. Satoru Kaneko

    Department of Obstetrics and Gynecology, Tokyo Dental College Ichikawa General Hospital, Ichikawa, Japan
    Competing interests
    The authors declare that no competing interests exist.
  4. Chikako Shimura

    Cellular Memory Laboratory, RIKEN, Wako, Japan
    Competing interests
    The authors declare that no competing interests exist.
  5. Yuki Okada

    Institute for Quantitative Biosciences, The University of Tokyo, Tokyo, Japan
    Competing interests
    The authors declare that no competing interests exist.
  6. Kenji Ichiyanagi

    Department of Animal Sciences, Nagoya University, Nagoya, Japan
    Competing interests
    The authors declare that no competing interests exist.
  7. Yoichi Shinkai

    Cellular Memory Laboratory, RIKEN, Wako, Japan
    For correspondence
    yshinkai@riken.jp
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6051-2484

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.

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.

Reviewing Editor

  1. Deborah Bourc'his, Institut Curie, France

Publication history

  1. Preprint posted: May 19, 2021 (view preprint)
  2. Received: January 6, 2022
  3. Accepted: March 21, 2022
  4. Accepted Manuscript published: March 22, 2022 (version 1)
  5. 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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  1. Kei Fukuda
  2. Yoshinori Makino
  3. Satoru Kaneko
  4. Chikako Shimura
  5. Yuki Okada
  6. Kenji Ichiyanagi
  7. Yoichi Shinkai
(2022)
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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