Testis-specific H2B.W1 disrupts nucleosome integrity by reducing DNA–histone interactions

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.

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Publication Details

Journal
Nucleic Acids Research
Published
2024-09-26
DOI
https://doi.org/10.1093/nar/gkae825
Citations
20
Primary Topic
Genomics and Chromatin Dynamics
Type
article
Field-Weighted Citation Impact
4.68

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article

Testis-specific H2B.W1 disrupts nucleosome integrity by reducing DNA–histone interactions

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20 citations
Nucleic Acids Research
Genomics and Chromatin Dynamics
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article

Testis-specific H2B.W1 disrupts nucleosome integrity by reducing DNA–histone interactions

Thi Thuy Nguyen, Xulun Sun, Toyotaka Ishibashi, Mingxi Deng, Matthew Yu Hin Pang, Yuanliang Zhai, Dongbo Ding, Yan Yan, Yingyi Zhang, Yue Liu, Zhichun Xu
article en
20 citations

Abstract

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.

Nucleic Acids ResearchVol. 52(19)
Hong Kong University of Science and Technology (HK), HKUST Shenzhen Research Institute (CN), Guangzhou HKUST Fok Ying Tung Research Institute (CN), University of Hong Kong (HK)
National Science Foundation, National Natural Science Foundation of China, Innovation and Technology Fund, Science, Technology and Innovation Commission of Shenzhen Municipality
Openalex Percentile: Top 4%
Genomics and Chromatin Dynamics
4.68
DOIOpen Access PDFOpenAlex
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