The Novel H2B Variant, H2BW2, Destabilizes Nucleosomes and Regulates Gene Expression During Early Human Spermatogenesis
58 Pages Posted: 3 Nov 2022 Publication Status: Review CompleteMore...
During spermatogenesis, the histones are gradually replaced by testis-specific histone variants, transition proteins, and eventually protamines in the elongating spermatids. H2BW2 is a mammalian testis-specific variant of histone H2B, however its functional role remains unknown. Here, we solved the structure of H2BW2-containing nucleosomes and elucidated the underlying functions of this variant in human spermatogenesis. H2BW2 destabilizes the nucleosome by reducing interactions between H2A-H2B dimers and DNA through alternations of the nucleosome unwrapping and rewrapping rates. Such destabilization effects mainly originate from the extended N-terminus tail and a number of surface charge changes in the α2 helixregion of H2BW2. Importantly, we also found that H2BW2 is highly enriched in the TERRA promoter regions in human testis, and it is associated with high TERRA expression and longer telomeres. Our results suggest that H2BW2 participates in the maintenance of telomere length by upregulating TERRA expression in early spermatogenesis.
Funding Information: This work was supported grants from the Hong Kong Innovation & Technology Commission Innovation and Technology Fund [MHP/033/20] and the National Science Foundation of China  awarded to T.I., and grants from the Research Grants Council of the Hong Kong SAR [C7009-20G, C6036-21GF] awarded to Y.Z. and T.I..
Conflict of Interests: The authors declare no competing interests.
Keywords: histone variant, spermatogenesis, testis-specific, telomere, TERRA, H2B
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