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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.<\/jats:p>","DOI":"10.1093\/nar\/gkae825","type":"journal-article","created":{"date-parts":[[2024,9,27]],"date-time":"2024-09-27T10:40:44Z","timestamp":1727433644000},"page":"11612-11625","source":"Crossref","is-referenced-by-count":23,"title":["Testis-specific H2B.W1 disrupts nucleosome integrity by reducing DNA\u2013histone interactions"],"prefix":"10.1093","volume":"52","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3515-8679","authenticated-orcid":false,"given":"Dongbo","family":"Ding","sequence":"first","affiliation":[{"name":"Division of Life Science, The Hong Kong University of Science and Technology , Clear Water Bay , NT , HKSAR ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3758-6140","authenticated-orcid":false,"given":"Matthew\u00a0Y H","family":"Pang","sequence":"additional","affiliation":[{"name":"Division of Life Science, The Hong Kong University of Science and Technology , Clear Water Bay , NT , HKSAR ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingxi","family":"Deng","sequence":"additional","affiliation":[{"name":"Division of Life Science, The Hong Kong University of Science and Technology , Clear Water Bay , NT , HKSAR ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thi\u00a0Thuy","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Division of Life Science, The Hong Kong University of Science and Technology , Clear Water Bay , NT , HKSAR ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Liu","sequence":"additional","affiliation":[{"name":"Division of Life Science, The Hong Kong University of Science and Technology , Clear Water Bay , NT , HKSAR ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xulun","family":"Sun","sequence":"additional","affiliation":[{"name":"Division of Life Science, The Hong Kong University of Science and Technology , Clear Water Bay , NT , HKSAR ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhichun","family":"Xu","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, The University of Hong Kong , Pokfulam , Hong Kong , HKSAR ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingyi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Biological Cryo-EM Center, The Hong Kong University of Science and Technology , Clear Water Bay , NT , HKSAR ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanliang","family":"Zhai","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, The University of Hong Kong , Pokfulam , Hong Kong , HKSAR ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3677-5006","authenticated-orcid":false,"given":"Yan","family":"Yan","sequence":"additional","affiliation":[{"name":"Division of Life Science, The Hong Kong University of Science and Technology , Clear Water Bay , NT , HKSAR ,","place":["China"]},{"name":"Shenzhen PKU-HKUST Medical Center , Shenzhen,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8015-2319","authenticated-orcid":false,"given":"Toyotaka","family":"Ishibashi","sequence":"additional","affiliation":[{"name":"Division of Life Science, The Hong Kong University of Science and Technology , Clear Water Bay , NT , HKSAR ,","place":["China"]},{"name":"The Hong Kong University of Science and Technology Fok Ying Tung Research Institute , Nansha, Guangzhou,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,9,26]]},"reference":[{"key":"2024102814480205500_B1","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1038\/38444","article-title":"Crystal structure of the nucleosome core particle at 2.8 \u00c5 resolution","volume":"389","author":"Luger","year":"1997","journal-title":"Nature"},{"key":"2024102814480205500_B2","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1038\/nrm3382","article-title":"New insights into nucleosome and chromatin structure: an ordered state or a disordered affair?","volume":"13","author":"Luger","year":"2012","journal-title":"Nat. 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