Division of Life Science, The Hong Kong University of Science and Technology, Clear Water Bay, NT, HKSAR, China.
School of Biological Sciences, The University of Hong Kong, Pokfulam, Hong Kong, HKSAR, China.
Nucleic Acids Res. 2024 Oct 28;52(19):11612-11625. doi: 10.1093/nar/gkae825.
Multiple testis-specific histone variants are involved in the dynamic chromatin transitions during spermatogenesis. H2B.W1 (previously called H2BFWT) is an H2B variant specific to primate testis with hitherto unclear functions, although its single-nucleotide polymorphisms (SNPs) are closely associated with male non-obstructive infertility. Here, we found that H2B.W1 is only expressed in the mid-late spermatogonia stages, and H2B.W1 nucleosomes are defined by a more flexible structure originating from weakened interactions between histones and DNA. Furthermore, one of its SNPs, H2B.W1-H100R, which is associated with infertility, further destabilizes the nucleosomes and increases the nucleosome unwrapping rate by interfering with the R100 and H4 K91/R92 interaction. Our results suggest that destabilizing H2B.W1 containing nucleosomes might change the chromatin structure of spermatogonia, and that H2B.W1-H100R enhances the nucleosome-destabilizing effects, leading to infertility.
多种睾丸特异性组蛋白变体参与精子发生过程中的动态染色质转变。H2B.W1（以前称为 H2BFWT）是一种特异性存在于灵长类睾丸中的 H2B 变体，其功能尚不清楚，尽管其单核苷酸多态性（SNP）与男性非梗阻性不育密切相关。在这里，我们发现 H2B.W1 仅在中晚期精原细胞阶段表达，并且 H2B.W1 核小体的结构更灵活，这源于组蛋白与 DNA 之间的相互作用减弱。此外，与不育相关的 SNP 之一 H2B.W1-H100R 通过干扰 R100 和 H4 K91/R92 相互作用，进一步破坏核小体的稳定性并增加核小体解包速率。我们的结果表明，破坏含有 H2B.W1 的核小体可能会改变精原细胞的染色质结构，并且 H2B.W1-H100R 增强核小体的去稳定作用，导致不育。
