ArticlePLoS genetics2026
Argonaute proteins orchestrate Meiotic Sex Chromosome Inactivation and timing of the spermatogenic transcriptional program.
Article in PLoS genetics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Argonaute proteins (AGO) are best known for their role in microRNA-mediated post-transcriptional gene silencing. Here, we demonstrate that AGO3 and AGO4, but not AGO2, localize to the sex chromatin of pachytene spermatocytes, where they are required for the transcriptional silencing of XY-linked genes that characterizes Meiotic Sex Chromosome Inactivation (MSCI). Previous findings showed that deletion of Ago4 (Ago4-/-) mildly impairs MSCI and normal spermatozoa production. By contrast, loss of Ago3 (Ago3-/-) does not produce these defects, while combined deletion of Ago1, Ago3, and Ago4 (Ago413-/-) leads to severely reduced fertility, accompanied by disrupted autosomal and sex chromosome gene regulation and altered chromatin accessibility in spermatocytes. In Ago413-/- mice, premature overexpression of spermiogenesis genes during prophase I results in reduced sperm production, abnormal sperm morphology, and impaired fertilization capacity. Together, AGO3 and AGO4 act during prophase I to ensure the timely expression of meiosis-related genes during prophase I while maintaining repression of spermiogenesis-associated genes. These results indicate that AGO3 and AGO4 act in a coordinated fashion in the male germline to orchestrate cell progression in spermatogenesis through temporal regulation of autosomal and sex chromosome genes.
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