Recruitment of TEX15 by HUSH2 drives repression of multicopy gene families in fertility regulation

Chromatin-associated proteins are key regulators of fertility. While the testis-specific protein TEX15 and a HUSH2 component TASOR2 have established roles in early germ cells and somatic cells respectively, this study identifies their cooperative role during spermiogenesis. Postnatal loss of either TEX15 or TASOR2 in mice causes teratozoospermia without retrotransposon de-repression. Mechanistically, TEX15 complexes with TASOR2 but not its paralogue TASOR in the testis. The resulting TEX15-HUSH2 complex localizes to nuclear foci in round spermatids, particularly at XY chromatin, with TASOR2 acting as the recruiter. TASOR2 and MPP8 preferentially bind to multicopy gene families in round spermatids. Consequently, many of these families—including the X-linked H2al histone-like genes—are upregulated in both TEX15-deficient spermatids and TASOR2-deficient testis. Together, these findings show that the TEX15-HUSH2 complex represses multicopy gene families during spermiogenesis, revealing a molecular mechanism underlying postmeiotic repression of sex chromatin critical for male fertility. In this study, Yang et al showed that the TEX15-HUSH2 complex represses multicopy gene families in haploid spermatids. Their study revealed a molecular mechanism underlying postmeiotic repression of sex chromatin (PMSC) critical for male fertility.