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The combined action of CTCF and its testis-specific paralog BORIS is essential for spermatogenesis

Author

Listed:
  • Samuel Rivero-Hinojosa

    (National Institute of Allergy and Infectious Diseases, National Institutes of Health
    Center for Cancer and Immunology Research, Children’s National Research Institute)

  • Elena M. Pugacheva

    (National Institute of Allergy and Infectious Diseases, National Institutes of Health)

  • Sungyun Kang

    (National Institute of Allergy and Infectious Diseases, National Institutes of Health
    Indiana University)

  • Claudia Fabiola Méndez-Catalá

    (National Institute of Allergy and Infectious Diseases, National Institutes of Health
    National Autonomous University of Mexico (UNAM))

  • Alexander L. Kovalchuk

    (National Institute of Allergy and Infectious Diseases, National Institutes of Health)

  • Alexander V. Strunnikov

    (Guangzhou Institutes of Biomedicine and Health, Molecular Epigenetics Laboratory)

  • Dmitri Loukinov

    (National Institute of Allergy and Infectious Diseases, National Institutes of Health)

  • Jeannie T. Lee

    (Massachusetts General Hospital
    Harvard Medical School)

  • Victor V. Lobanenkov

    (National Institute of Allergy and Infectious Diseases, National Institutes of Health)

Abstract

CTCF is a key organizer of the 3D genome. Its specialized paralog, BORIS, heterodimerizes with CTCF but is expressed only in male germ cells and in cancer states. Unexpectedly, BORIS-null mice have only minimal germ cell defects. To understand the CTCF-BORIS relationship, mouse models with varied CTCF and BORIS levels were generated. Whereas Ctcf+/+Boris+/+, Ctcf+/−Boris+/+, and Ctcf+/+Boris−/− males are fertile, Ctcf+/−Boris−/− (Compound Mutant; CM) males are sterile. Testes with combined depletion of both CTCF and BORIS show reduced size, defective meiotic recombination, increased apoptosis, and malformed spermatozoa. Although CM germ cells exhibit only 25% of CTCF WT expression, chromatin binding of CTCF is preferentially lost from CTCF-BORIS heterodimeric sites. Furthermore, CM testes lose the expression of a large number of spermatogenesis genes and gain the expression of developmentally inappropriate genes that are “toxic” to fertility. Thus, a combined action of CTCF and BORIS is required to both repress pre-meiotic genes and activate post-meiotic genes for a complete spermatogenesis program.

Suggested Citation

  • Samuel Rivero-Hinojosa & Elena M. Pugacheva & Sungyun Kang & Claudia Fabiola Méndez-Catalá & Alexander L. Kovalchuk & Alexander V. Strunnikov & Dmitri Loukinov & Jeannie T. Lee & Victor V. Lobanenkov, 2021. "The combined action of CTCF and its testis-specific paralog BORIS is essential for spermatogenesis," Nature Communications, Nature, vol. 12(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-24140-6
    DOI: 10.1038/s41467-021-24140-6
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    Cited by:

    1. Ke Song & Xinyan Yang & Geng An & Xinyu Xia & Jiexiang Zhao & Xiaoheng Xu & Cong Wan & Tianyuan Liu & Yi Zheng & Shaofang Ren & Mei Wang & Gang Chang & Shane J. F. Cronin & Josef M. Penninger & Tao Ji, 2022. "Targeting APLN/APJ restores blood-testis barrier and improves spermatogenesis in murine and human diabetic models," Nature Communications, Nature, vol. 13(1), pages 1-17, December.

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