Endogenous retroviruses drive species-specific germline transcriptomes in mammals

• Published in: Nature structural & molecular biology Vol. 27; no. 10; pp. 967 - 977
• Main Authors: Sakashita, Akihiko, Maezawa, So, Takahashi, Kazuki, Alavattam, Kris G., Yukawa, Masashi, Hu, Yueh-Chiang, Kojima, Shohei, Parrish, Nicholas F., Barski, Artem, Pavlicev, Mihaela, Namekawa, Satoshi H.
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.10.2020
• Subjects: 13/100; 14/1; 14/63; 38/22; 38/23; 38/39; 38/77; 631/136; 631/208/177; 64/60; Animals; Biochemistry; Biological Microscopy; Biomedical and Life Sciences; Chromatin - genetics; Chromatin - virology; Endogenous Retroviruses - genetics; Enhancer Elements, Genetic; Gene Expression Regulation, Viral; Humans; Life Sciences; Long Interspersed Nucleotide Elements; Male; Mammals - genetics; Mammals - virology; Meiosis; Membrane Biology; Mice, Inbred C57BL; Mice, Transgenic; Mitosis; Mutation; Protein Structure; Proto-Oncogene Proteins c-myb - genetics; Repetitive Sequences, Nucleic Acid; Rodentia - genetics; Rodentia - virology; Spermatogenesis - genetics; Spermatozoa - physiology; Spermatozoa - virology; Trans-Activators - genetics; Transcriptome
• ISSN: 1545-9993; 1545-9985; 1545-9985
• DOI: 10.1038/s41594-020-0487-4

Gene regulation in the germline ensures the production of high-quality gametes, long-term maintenance of the species and speciation. Male germline transcriptomes undergo dynamic changes after the mitosis-to-meiosis transition and have been subject to evolutionary divergence among mammals. However, the mechanisms underlying germline regulatory divergence remain undetermined. Here, we show that endogenous retroviruses (ERVs) influence species-specific germline transcriptomes. After the mitosis-to-meiosis transition in male mice, specific ERVs function as active enhancers to drive germline genes, including a mouse-specific gene set, and bear binding motifs for critical regulators of spermatogenesis, such as A-MYB. This raises the possibility that a genome-wide transposition of ERVs rewired germline gene expression in a species-specific manner. Of note, independently evolved ERVs are associated with the expression of human-specific germline genes, demonstrating the prevalence of ERV-driven mechanisms in mammals. Together, we propose that ERVs fine-tune species-specific transcriptomes in the mammalian germline. ERV-specific enhancer-based networks regulate species-specific transcriptomes in mammalian spermatogenesis.