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Histone H2B type W-T (H2B.W1) is a primate- and testis-specific histone H2B variant protein encoded by the H2BW1 gene on the X chromosome[2][3][4][5]. Unlike canonical H2B, H2B.W1 is selectively expressed during the mid- to late-spermatogonia stages of spermatogenesis and is predominantly found in sperm nuclei. It incorporates into nucleosomes, resulting in nucleosome structures with greater DNA flexibility and decreased stability due to reduced DNA–histone interactions. This structural property is proposed to facilitate chromatin remodeling and open chromatin states required for specific developmental processes in spermatogenesis. H2B.W1 does not participate in mitotic chromosome condensation due to its divergent N-terminal tail structure. Certain polymorphisms in H2BW1, notably H100R, are strongly associated with male non-obstructive infertility; these variants further destabilize nucleosomes and may interfere with proper chromatin organization and gene regulation in sperm development. There are no established therapeutic drugs targeting H2B.W1, and it is not currently considered a druggable clinical target[1][3][4][5].
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