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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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Autores principales: Fukuda, Kei, Makino, Yoshinori, Kaneko, Satoru, Shimura, Chikako, Okada, Yuki, Ichiyanagi, Kenji, Shinkai, Yoichi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8967385/
https://www.ncbi.nlm.nih.gov/pubmed/35315771
http://dx.doi.org/10.7554/eLife.76822
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author Fukuda, Kei
Makino, Yoshinori
Kaneko, Satoru
Shimura, Chikako
Okada, Yuki
Ichiyanagi, Kenji
Shinkai, Yoichi
author_facet Fukuda, Kei
Makino, Yoshinori
Kaneko, Satoru
Shimura, Chikako
Okada, Yuki
Ichiyanagi, Kenji
Shinkai, Yoichi
author_sort Fukuda, Kei
collection PubMed
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 pubmed-89673852022-03-31 Potential role of KRAB-ZFP binding and transcriptional states on DNA methylation of retroelements in human male germ cells Fukuda, Kei Makino, Yoshinori Kaneko, Satoru Shimura, Chikako Okada, Yuki Ichiyanagi, Kenji Shinkai, Yoichi eLife Chromosomes and Gene Expression 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. eLife Sciences Publications, Ltd 2022-03-22 /pmc/articles/PMC8967385/ /pubmed/35315771 http://dx.doi.org/10.7554/eLife.76822 Text en © 2022, Fukuda et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Chromosomes and Gene Expression
Fukuda, Kei
Makino, Yoshinori
Kaneko, Satoru
Shimura, Chikako
Okada, Yuki
Ichiyanagi, Kenji
Shinkai, Yoichi
Potential role of KRAB-ZFP binding and transcriptional states on DNA methylation of retroelements in 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 Chromosomes and Gene Expression
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8967385/
https://www.ncbi.nlm.nih.gov/pubmed/35315771
http://dx.doi.org/10.7554/eLife.76822
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