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While several of these variants have been characterized, the role of H2B.W2, a member of the H2BW family, remains largely unclear. Here, we showed that H2B.W2 expression occurs mainly in spermatocytes, slightly later than its paralog H2B.W1. Cryo-electron microscopy\u00a0analysis of H2B.W2-containing nucleosomes reveals a more relaxed conformation compared to canonical nucleosomes caused by weakened interactions between the outer DNA turn and the histone core. We pinpointed the N-terminal tail and \u03b12 helix of H2B.W2 as critical regions for nucleosome destabilization. Furthermore, we identify G73 within the L1 loop as a key residue involved in disrupting higher-order chromatin structure. Our findings suggest that H2B.W2-mediated nucleosome and chromatin destabilization may play a role in regulating gene expression during spermatogenesis, with potential implications for sperm development and function.<\/jats:p>","DOI":"10.1093\/nar\/gkaf825","type":"journal-article","created":{"date-parts":[[2025,8,28]],"date-time":"2025-08-28T10:42:42Z","timestamp":1756377762000},"source":"Crossref","is-referenced-by-count":2,"title":["H2B.W2, a spermatocyte-specific histone variant, disrupts nucleosome stability, and reduces chromatin compaction"],"prefix":"10.1093","volume":"53","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5584-1013","authenticated-orcid":false,"given":"April T T","family":"Nguyen","sequence":"first","affiliation":[{"name":"Division of Life Science, The Hong Kong University of Science and Technology, Clear Water Bay, NT , HKSAR ,\u00a0","place":["China"]},{"name":"Centre for Translational Stem Cell Biology, Hong Kong Science and Technology Park Present\u00a0address: , Shatin,\u00a0New Territories, Hong Kong , HKSAR ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3515-8679","authenticated-orcid":false,"given":"Dongbo","family":"Ding","sequence":"additional","affiliation":[{"name":"Division of Life Science, The Hong Kong University of Science and Technology, Clear Water Bay, NT , HKSAR ,\u00a0","place":["China"]},{"name":"Institute of Biophysics, Chinese Academy of Science Present\u00a0address: , Chaoyang,\u00a0Beijing\u00a0100101 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinpeng","family":"Bai","sequence":"additional","affiliation":[{"name":"Division of Life Science, The Hong Kong University of Science and Technology, Clear Water Bay, NT , HKSAR ,\u00a0","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3758-6140","authenticated-orcid":false,"given":"Matthew Y H","family":"Pang","sequence":"additional","affiliation":[{"name":"Division of Life Science, The Hong Kong University of Science and Technology, Clear Water Bay, NT , HKSAR ,\u00a0","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 ,\u00a0","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 ,\u00a0","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingyu","family":"Jin","sequence":"additional","affiliation":[{"name":"Division of Life Science, The Hong Kong University of Science and Technology, Clear Water Bay, NT , HKSAR ,\u00a0","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 ,\u00a0","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 ,\u00a0 Clear Water Bay, NT, HKSAR ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8897-6416","authenticated-orcid":false,"given":"Yuanliang","family":"Zhai","sequence":"additional","affiliation":[{"name":"Division of Life Science, The Hong Kong University of Science and Technology, Clear Water Bay, NT , HKSAR ,\u00a0","place":["China"]},{"name":"School of Biological Sciences, The University of Hong Kong , Pokfulam, Hong Kong, HKSAR ,\u00a0","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"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 ,\u00a0","place":["China"]},{"name":"Shenzhen Peking University,\u00a0The Hong Kong University of Science and Technology Medical Center , Shenzhen, Guangzhou 518055 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