Genome biology · 2026
Conserved enhancer association of piRNAs and the implication in germ cell fate surveillance.
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Kung Pin-Jui, Tsai Yi-Tzang, Chungunco Gabrielle Marie Limpe, Chang Kai-Wei, Lin Hsien-Hen, Zhou Sheng-Jia Johnson, Tseng Yen-Tzu, Cheng Luca Ching-Wen, Liao Hung-Fu, Ju Yan-Ru, Chung Ching-Yu, Kuo Hung-Chih, Namekawa Satoshi H, Ho Hong-Nerng, Chen Hsin-Fu, Laird Diana J, Lin Shau-Ping
Аннотация
BACKGROUND: The PIWI-piRNA pathway is crucial for protecting genomic integrity from derepressed transposon invasion in developing germ cells after genome-wide epigenetic erasure. While extensive mouse studies show that pre-pachytene piRNAs contribute to establishing the epigenetic landscape, little is known about human piRNAs during embryonic fetal germ cell development. In this study, we collect fetal testes of gestational week 12-22 abortuses from Taiwan, to investigate human piRNA profiles correlating to the time window of epigenetic landscape establishment together with those generated from USA samples.
RESULTS: We identify numerous human piRNAs in second-trimester fetal testes that corresponded to small nucleolar RNAs. Remarkably, a substantial proportion of human fetal testicular piRNAs map to super-enhancers and typical enhancers. This piRNA-enhancer association is a highly conserved phenomenon across diverse amniote species, including humans, mice, and chickens.
CONCLUSIONS: Notably, many of the pre-pachytene germline piRNAs mapped to enhancers usually active in various somatic lineages. We propose a conserved biological role for these piRNAs: they actively regulate enhancer activity and modulate enhancerRNA (eRNA) turnover. This dosage-dependent piRNA surveillance provides a critical layer of post-specification regulation, actively repressing untimely somatic gene expression to safeguard and maintain germ cell identity.
RESULTS: We identify numerous human piRNAs in second-trimester fetal testes that corresponded to small nucleolar RNAs. Remarkably, a substantial proportion of human fetal testicular piRNAs map to super-enhancers and typical enhancers. This piRNA-enhancer association is a highly conserved phenomenon across diverse amniote species, including humans, mice, and chickens.
CONCLUSIONS: Notably, many of the pre-pachytene germline piRNAs mapped to enhancers usually active in various somatic lineages. We propose a conserved biological role for these piRNAs: they actively regulate enhancer activity and modulate enhancerRNA (eRNA) turnover. This dosage-dependent piRNA surveillance provides a critical layer of post-specification regulation, actively repressing untimely somatic gene expression to safeguard and maintain germ cell identity.