Conserved enhancer association of piRNAs and the implication in germ cell fate surveillance

The PIWI-piRNA pathway is crucial for protecting genomic integrity from derepressed transposon invasion in developing germ cells after genome-wide epigenetic erasure. Extensive mouse studies show that pre-pachytene piRNAs contribute to establishing the epigenetic landscape. However, little is known about human piRNAs during embryonic fetal germ cell development. In this study, we collected fetal testes of gestational week 12–22 abortuses from Taiwan and the USA, to investigate human piRNA profiles correlating to the time window of epigenetic landscape establishment. We identified numerous human piRNAs in second-trimester fetal testes that corresponded to small nucleolar RNAs. Additionally, a substantial proportion of human fetal testicular piRNAs mapped to super-enhancers and typical enhancers, a phenomenon conserved across mouse and chicken species. Notably, many of the pre-pachytene germline piRNAs mapped to enhancers active in various adult somatic lineages, implying they may regulate enhancer activities and safeguard germ cell identity by reducing aberrant expression of somatic genes.