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Testis-specific H2B.W1 disrupts nucleosome integrity by reducing DNA-histone interactions
Dongbo Ding1, Matthew Y H Pang1, Mingxi Deng1
1Division of Life Science, The Hong Kong University of Science and Technology, Clear Water Bay, NT, HKSAR, China.
Nucleic Acids Research
|September 27, 2024
Summary
Testis-specific histone H2B.W1 plays a role in spermatogenesis. Its destabilization by single-nucleotide polymorphisms (SNPs) is linked to male infertility by altering chromatin structure.
Area of Science:
- Reproductive Biology
- Chromatin Biology
- Genetics
Background:
- Spermatogenesis involves dynamic chromatin remodeling mediated by testis-specific histone variants.
- H2B.W1 is a primate-specific H2B variant with poorly understood functions.
- Single-nucleotide polymorphisms (SNPs) in H2B.W1 are linked to male non-obstructive infertility.
Purpose of the Study:
- To investigate the function and structural properties of H2B.W1 during spermatogenesis.
- To elucidate the impact of H2B.W1 SNPs on nucleosome stability and chromatin structure.
- To understand the molecular mechanisms underlying H2B.W1-associated male infertility.
Main Methods:
- Analysis of H2B.W1 expression patterns during spermatogenesis.
- Biophysical characterization of H2B.W1 nucleosomes.
- Investigation of SNP effects on histone-DNA and histone-histone interactions.
Main Results:
- H2B.W1 is expressed in mid-late spermatogonia stages.
- H2B.W1 nucleosomes exhibit increased flexibility due to weakened histone-DNA interactions.
- The H2B.W1-H100R SNP destabilizes nucleosomes and increases DNA unwrapping by disrupting H4 K91/R92 interactions.
Conclusions:
- Destabilization of H2B.W1 nucleosomes may alter spermatogonial chromatin structure.
- The H2B.W1-H100R SNP exacerbates nucleosome destabilization, contributing to male infertility.
- H2B.W1 and its variants are critical for maintaining male fertility through proper chromatin regulation.
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