Journal
ELIFE
Volume 11, Issue -, Pages -Publisher
eLIFE SCIENCES PUBL LTD
DOI: 10.7554/eLife.76822
Keywords
retroelements; DNA methylation; human male germ cells; Human
Categories
Funding
- Special Postdoctoral Researcher (SPDR) Program of RIKEN
- Japan Ministry of Education, Culture, Sports, Science, and Technology [18H05530, 18H03991]
- Grants-in-Aid for Scientific Research [18H03991, 18H05530] Funding Source: KAKEN
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The Kruppel-associated box domain zinc finger proteins are associated with DNA methylation of retroelements in human primordial germ cells, and during human spermatogenesis, the hominoid-specific retroelement SINE-VNTR-Alus (SVA) may undergo transcription-directed de novo DNA methylation, leading to significant inter-individual epigenetic variation in sperm.
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 Kruppel-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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