H2B.W2, a Spermatocytes-specific Histone Variant, disrupts nucleosome stability and reduces chromatin compaction

NGUYEN, T. T.; Ding, D.; Bai, X.; Pang, M. Y. H.; Mingxi, D.; Liu, Y.; Jin, T.; Zhichun, X.; Zhang, Y.; Zhai, Y.; Yan, Y.; Ishibashi, T.

doi:10.1101/2024.12.12.626759

bioRxiv · 10.1101/2024.12.12.626759

H2B.W2, a Spermatocytes-specific Histone Variant, disrupts nucleosome stability and reduces chromatin compaction

NGUYEN, T. T.·Ding, D.·Bai, X.·Pang, M. Y. H.·Mingxi, D.·Liu, Y.·Jin, T.·Zhichun, X.·Zhang, Y.·Zhai, Y.·Yan, Y.·Ishibashi, T.

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Abstract

Spermatogenesis is a highly regulated process that requires precise chromatin remodeling, which includes the incorporation of testis-specific histone variants. 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 (cryo-EM) analysis 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 2 helix of H2B.W2, specifically residues D85 and Q101, as critical 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.

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NGUYEN, T. T., Ding, D., Bai, X., Pang, M. Y. H., Mingxi, D., Liu, Y., Jin, T., Zhichun, X., Zhang, Y., Zhai, Y., Yan, Y., Ishibashi, T.. 2024-12-13. H2B.W2, a Spermatocytes-specific Histone Variant, disrupts nucleosome stability and reduces chromatin compaction. https://doi.org/10.1101/2024.12.12.626759

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