Research scientist University of Pennsylvania philadelphila, Pennsylvania, United States
Abstract Authors: Fang Yang1, Zhenlong Kang1, N. Adrian Leu1, and P. Jeremy Wang1
1Department of Biomedical Sciences, University of Pennsylvania, Philadelphia, Pennsylvania, US.
Abstract Text: In mouse spermiogenesis, round spermatids undergo extensive morphological changes to transform into elongated spermatids with a sickle head and a tail. Both head and tail are essential for fertilization. Manchette, a transient microtubular platform, appears in step 8 round spermatids and disappears in step 13-14 elongating spermatids, plays an important role in sperm head morphogenesis and tail formation. Meanwhile, canonical histones are replaced by transition proteins and then by protamines which compact nucleus by six-fold. Only 1% of histones are retained in mouse epididymal sperm. Many chromatin factors contribute to this differentiation process. We previously reported that TEX15, a testis-specific protein, is essential for retrotransposon silencing and meiotic progression in male germ cells. Here we report that the DUF3715 domain in TEX15 is required for retrotransposon silencing. Importantly, we found that TEX15 plays a novel role in spermiogenesis. Postnatal inactivation of TEX15 leads to abnormal mushroom head morphology in sperm and male subfertility but not de-repression of retrotransposons. TEX15 is associated with TASOR2 and MPP8 but not TASOR in postnatal testis. TASOR2, sharing the DUF3715 domain with TASOR and TEX15, gradually forms large aggregates in the nuclei from step 2 to step 8 round spermatids right before spermatid nuclear condensation. Both TEX15 and MPP8 localize to TASOR2 foci in the nuclei of round spermatids. While the formation of TASOR2 and MPP8 foci is independent of TEX15, the formation of TEX15 and MPP8 foci is dependent on TASOR2. TASOR2 knockout sperm also displayed abnormal head shape, resulting in subfertility. However, manchette and tail are formed normally and histones are not significantly retained in sperm from either mutant. In the future, we plan to carry out RNA-seq and ChIP-seq analyses of mutant round spermatids and characterize new TEX15-interacting proteins to elucidate the function of TEX15 and TASOR2 in spermiogenesis. In summary, TEX15 plays an important role in spermiogenesis through interaction with a distinct HUSH2 complex (TASOR2-MPP8-PPHLN1).
