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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Published in:eLife 2022-03, Vol.11
Main Authors: Fukuda, Kei, Makino, Yoshinori, Kaneko, Satoru, Shimura, Chikako, Okada, Yuki, Ichiyanagi, Kenji, Shinkai, Yoichi
Format: Article
Language:English
Subjects:
Animals
Chromosomes and Gene Expression
DNA
DNA binding proteins
DNA Methylation
Epigenetic inheritance
Epigenetics
Epigenomics
Genetic aspects
Genetic transcription
Genetics and Genomics
Genomes
Germ cells
Germ Cells - metabolism
Histones
human male germ cells
Humans
Male
Male sterility
Mammals - genetics
Methylation
Mice
Molecular modelling
retroelements
Retroelements - genetics
Sperm
Spermatogenesis
Spermatogenesis - genetics
Stem cells
Transcription
Zinc finger proteins
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Summary: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- (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.
ISSN:2050-084X
2050-084X
DOI:10.7554/elife.76822