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The Novel H2B Variant, H2BW2, Destabilizes Nucleosomes and Regulates Gene Expression During Early Human Spermatogenesis

58 Pages Posted: 3 Nov 2022 Publication Status: Review Complete

See all articles by Thi Thuy Nguyen

Thi Thuy Nguyen

Hong Kong University of Science & Technology (HKUST) - Division of Life Science

Dongbo Ding

Hong Kong University of Science & Technology (HKUST) - Division of Life Science

Matthew Y. H. Pang

Hong Kong University of Science & Technology (HKUST) - Division of Life Science

Mingxi Deng

Hong Kong University of Science & Technology (HKUST) - Division of Life Science

Zhichun Xu

The University of Hong Kong - School of Biological Sciences

Yingyi Zhang

Hong Kong University of Science & Technology (HKUST) - Division of Life Science

Yuanliang Zhai

The University of Hong Kong - School of Biological Sciences

Yan Yan

Hong Kong University of Science & Technology (HKUST) - Division of Life Science

Toyotaka Ishibashi

Hong Kong University of Science & Technology (HKUST) - Division of Life Science

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Abstract

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 [32170548] 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

Suggested Citation

Nguyen, Thi Thuy and Ding, Dongbo and Pang, Matthew Y. H. and Deng, Mingxi and Xu, Zhichun and Zhang, Yingyi and Zhai, Yuanliang and Yan, Yan and Ishibashi, Toyotaka, The Novel H2B Variant, H2BW2, Destabilizes Nucleosomes and Regulates Gene Expression During Early Human Spermatogenesis. Available at SSRN: https://ssrn.com/abstract=4261557 or http://dx.doi.org/10.2139/ssrn.4261557
This version of the paper has not been formally peer reviewed.

Thi Thuy Nguyen

Hong Kong University of Science & Technology (HKUST) - Division of Life Science ( email )

Dongbo Ding

Hong Kong University of Science & Technology (HKUST) - Division of Life Science ( email )

Matthew Y. H. Pang

Hong Kong University of Science & Technology (HKUST) - Division of Life Science ( email )

Mingxi Deng

Hong Kong University of Science & Technology (HKUST) - Division of Life Science ( email )

Zhichun Xu

The University of Hong Kong - School of Biological Sciences ( email )

Yingyi Zhang

Hong Kong University of Science & Technology (HKUST) - Division of Life Science ( email )

Yuanliang Zhai

The University of Hong Kong - School of Biological Sciences ( email )

Yan Yan

Hong Kong University of Science & Technology (HKUST) - Division of Life Science ( email )

Toyotaka Ishibashi (Contact Author)

Hong Kong University of Science & Technology (HKUST) - Division of Life Science ( email )

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