Potential role of KRAB-ZFP binding and transcriptional states on DNA methylation of retroelements in human male germ cells

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 studi...

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Main Authors: Kei Fukuda, Yoshinori Makino, Satoru Kaneko, Chikako Shimura, Yuki Okada, Kenji Ichiyanagi, Yoichi Shinkai
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2022-03-01
Series:eLife
Subjects:
Online Access:https://elifesciences.org/articles/76822
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author Kei Fukuda
Yoshinori Makino
Satoru Kaneko
Chikako Shimura
Yuki Okada
Kenji Ichiyanagi
Yoichi Shinkai
author_facet Kei Fukuda
Yoshinori Makino
Satoru Kaneko
Chikako Shimura
Yuki Okada
Kenji Ichiyanagi
Yoichi Shinkai
author_sort Kei Fukuda
collection DOAJ
description 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 are associated with DNA methylation of retroelements in human primordial germ cells. 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.
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spelling doaj.art-ede302e6533b4adfa10cd77f596ff1442022-12-22T03:33:56ZengeLife Sciences Publications LtdeLife2050-084X2022-03-011110.7554/eLife.76822Potential role of KRAB-ZFP binding and transcriptional states on DNA methylation of retroelements in human male germ cellsKei Fukuda0https://orcid.org/0000-0002-4111-9409Yoshinori Makino1Satoru Kaneko2Chikako Shimura3Yuki Okada4Kenji Ichiyanagi5Yoichi Shinkai6https://orcid.org/0000-0002-6051-2484Cellular Memory Laboratory, RIKEN Cluster for Pioneering Research, Wako, JapanLaboratory of Pathology and Development, Institute for Quantitative Biosciences, The University of Tokyo, Tokyo, JapanDepartment of Obstetrics and Gynecology, Ichikawa General Hospital, Tokyo Dental College, Ichikawa, JapanCellular Memory Laboratory, RIKEN Cluster for Pioneering Research, Wako, JapanLaboratory of Pathology and Development, Institute for Quantitative Biosciences, The University of Tokyo, Tokyo, JapanLaboratory of Genome and Epigenome Dynamics, Department of Animal Sciences, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, JapanCellular Memory Laboratory, RIKEN Cluster for Pioneering Research, Wako, JapanDNA 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 are associated with DNA methylation of retroelements in human primordial germ cells. 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.https://elifesciences.org/articles/76822retroelementsDNA methylationhuman male germ cells
spellingShingle Kei Fukuda
Yoshinori Makino
Satoru Kaneko
Chikako Shimura
Yuki Okada
Kenji Ichiyanagi
Yoichi Shinkai
Potential role of KRAB-ZFP binding and transcriptional states on DNA methylation of retroelements in human male germ cells
eLife
retroelements
DNA methylation
human male germ cells
title Potential role of KRAB-ZFP binding and transcriptional states on DNA methylation of retroelements in human male germ cells
title_full Potential role of KRAB-ZFP binding and transcriptional states on DNA methylation of retroelements in human male germ cells
title_fullStr Potential role of KRAB-ZFP binding and transcriptional states on DNA methylation of retroelements in human male germ cells
title_full_unstemmed Potential role of KRAB-ZFP binding and transcriptional states on DNA methylation of retroelements in human male germ cells
title_short Potential role of KRAB-ZFP binding and transcriptional states on DNA methylation of retroelements in human male germ cells
title_sort potential role of krab zfp binding and transcriptional states on dna methylation of retroelements in human male germ cells
topic retroelements
DNA methylation
human male germ cells
url https://elifesciences.org/articles/76822
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