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Chd5 orchestrates chromatin remodelling during sperm development

Author

Listed:
  • Wangzhi Li

    (Cold Spring Harbor Laboratory
    Molecular and Cellular Biology Program, Stony Brook University)

  • Jie Wu

    (Cold Spring Harbor Laboratory
    Stony Brook University)

  • Sang-Yong Kim

    (Cold Spring Harbor Laboratory)

  • Ming Zhao

    (MD Anderson Cancer Center)

  • Stephen A. Hearn

    (Cold Spring Harbor Laboratory)

  • Michael Q. Zhang

    (Center for Systems Biology, The University of Texas at Dallas
    Center for Synthetic and System Biology, Tsinghua University)

  • Marvin L. Meistrich

    (MD Anderson Cancer Center)

  • Alea A. Mills

    (Cold Spring Harbor Laboratory)

Abstract

One of the most remarkable chromatin remodelling processes occurs during spermiogenesis, the post-meiotic phase of sperm development during which histones are replaced with sperm-specific protamines to repackage the genome into the highly compact chromatin structure of mature sperm. Here we identify Chromodomain helicase DNA binding protein 5 (Chd5) as a master regulator of the histone-to-protamine chromatin remodelling process. Chd5 deficiency leads to defective sperm chromatin compaction and male infertility in mice, mirroring the observation of low CHD5 expression in testes of infertile men. Chd5 orchestrates a cascade of molecular events required for histone removal and replacement, including histone 4 (H4) hyperacetylation, histone variant expression, nucleosome eviction and DNA damage repair. Chd5 deficiency also perturbs expression of transition proteins (Tnp1/Tnp2) and protamines (Prm1/2). These findings define Chd5 as a multi-faceted mediator of histone-to-protamine replacement and depict the cascade of molecular events underlying this process of extensive chromatin remodelling.

Suggested Citation

  • Wangzhi Li & Jie Wu & Sang-Yong Kim & Ming Zhao & Stephen A. Hearn & Michael Q. Zhang & Marvin L. Meistrich & Alea A. Mills, 2014. "Chd5 orchestrates chromatin remodelling during sperm development," Nature Communications, Nature, vol. 5(1), pages 1-15, September.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms4812
    DOI: 10.1038/ncomms4812
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    Cited by:

    1. Nur Afizah Yusoff & Siti Balkis Budin & Izatus Shima Taib, 2017. "Pesticide Exposures Induce Male-Mediated Reproductive Toxicity: A Review," Journal of Agricultural Science, Canadian Center of Science and Education, vol. 9(13), pages 122-122, December.

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