Amplicon-seq of SVA methylation in human sperm

DNA methylation, repressive histone modifications, and PIWI-interacting RNA are essential for controlling retroelement silencing in the mammalian germ line. Dysregulation of retroelement silencing is associated with male sterility. Although DNA methylation 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), and hominoid-specific retroelement SINE-VNTR-Alus (SVA) is subjected to transcription-directed de novo DNA methylation during human spermatogenesis. Furthermore, we show that the degree of de novo DNA methylation in SVAs varies among human individuals, which confers a major inter-individual epigenetic variation in sperm. Collectively, our results provide potential molecular mechanisms of how retroelements are regulated during human male germ cells Overall design: Examination of DNA methylation of SVA transposons from five sperm donors