KRAB zinc-finger proteins regulate endogenous retroviruses to sculpt germline transcriptomes and genome evolution
- 1Department of Microbiology and Molecular Genetics, University of California, Davis, California 95616, USA;
- 2Department of Applied Biological Science, Faculty of Science and Technology, Tokyo University of Science, Noda, Chiba 278-8510, Japan;
- 3Reproductive Sciences Center, Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA;
- 4Department of Molecular Biology, Keio University School of Medicine, Tokyo 160-8582, Japan;
- 5Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
Abstract
As transposable elements (TEs) coevolved with the host genome, the host genome exploited TEs as functional regulatory elements of gene expression. Here we show that a subset of KRAB domain–containing zinc-finger proteins (KZFPs), which are highly expressed in mitotically dividing spermatogonia, repress the enhancer function of endogenous retroviruses (ERVs) and that the release from KZFP-mediated repression allows activation of ERV enhancers upon entry into meiosis. This regulatory feature is observed for independently evolved KZFPs and ERVs in mice and humans, suggesting evolutionary conservation in mammals. Further, we show that KZFP-targeted ERVs are underrepresented on the sex chromosomes in meiosis, suggesting that meiotic sex chromosome inactivation (MSCI) may antagonize the coevolution of KZFPs and ERVs in mammals. Our study uncovers a mechanism by which a subset of KZFPs regulate ERVs to sculpt germline transcriptomes. We propose that epigenetic programming during the transition from mitotic spermatogonia to meiotic spermatocytes facilitates the coevolution of KZFPs and TEs on autosomes and is antagonized by MSCI.
Footnotes
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[Supplemental material is available for this article.]
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Article published online before print. Article, supplemental material, and publication date are at https://www.genome.org/cgi/doi/10.1101/gr.279924.124.
- Received August 13, 2024.
- Accepted February 6, 2025.
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