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TitleTestis-specific H2B.W1 disrupts nucleosome integrity by reducing DNA-histone interactions.
Journal, issue, pagesNucleic Acids Res, Vol. 52, Issue 19, Page 11612-11625, Year 2024
Publish dateOct 28, 2024
AuthorsDongbo Ding / Matthew Y H Pang / Mingxi Deng / Thi Thuy Nguyen / Yue Liu / Xulun Sun / Zhichun Xu / Yingyi Zhang / Yuanliang Zhai / Yan Yan / Toyotaka Ishibashi /
PubMed AbstractMultiple testis-specific histone variants are involved in the dynamic chromatin transitions during spermatogenesis. H2B.W1 (previously called H2BFWT) is an H2B variant specific to primate testis with ...Multiple testis-specific histone variants are involved in the dynamic chromatin transitions during spermatogenesis. H2B.W1 (previously called H2BFWT) is an H2B variant specific to primate testis with hitherto unclear functions, although its single-nucleotide polymorphisms (SNPs) are closely associated with male non-obstructive infertility. Here, we found that H2B.W1 is only expressed in the mid-late spermatogonia stages, and H2B.W1 nucleosomes are defined by a more flexible structure originating from weakened interactions between histones and DNA. Furthermore, one of its SNPs, H2B.W1-H100R, which is associated with infertility, further destabilizes the nucleosomes and increases the nucleosome unwrapping rate by interfering with the R100 and H4 K91/R92 interaction. Our results suggest that destabilizing H2B.W1 containing nucleosomes might change the chromatin structure of spermatogonia, and that H2B.W1-H100R enhances the nucleosome-destabilizing effects, leading to infertility.
External linksNucleic Acids Res / PubMed:39329259 / PubMed Central
MethodsEM (single particle)
Resolution3.14 - 3.42 Å
Structure data

36148

8jbx

EMDB-36148, PDB-8jbx:
Human canonical 601 DNA nucleosome
Method: EM (single particle) / Resolution: 3.35 Å

36157

8jcc

EMDB-36157, PDB-8jcc:
Human histone H2B variant H2BFWT Cryo-EM structure with 601 DNA sequence
Method: EM (single particle) / Resolution: 3.42 Å

36158

8jcd

EMDB-36158, PDB-8jcd:
Human H2BFWTH100R nucleosome with 601 DNA
Method: EM (single particle) / Resolution: 3.14 Å

Source
  • homo sapiens (human)
  • synthetic construct (others)
KeywordsDNA BINDING PROTEIN/DNA / Histone / Nucleosome / DNA BINDING PROTEIN / DNA BINDING PROTEIN-DNA complex / histone variant

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