• A novel gene involved in male infertilit

    From ScienceDaily@1:317/3 to All on Tue Aug 24 21:30:40 2021
    A novel gene involved in male infertility: ZFP541
    Understanding the mechanisms that control the expression of meiosis-
    related genes

    Date:
    August 24, 2021
    Source:
    Kumamoto University
    Summary:
    A new gene that controls the completion of meiosis in
    spermatogenesis has been discovered. Until now, details of the
    mechanism that inactivates the expression of genes involved in the
    meiotic program during spermatogenesis had not been clarified. The
    researchers believe that this may lead to an advancement in
    reproductive medicine, like identifying causes for infertility
    from azoospermia or spermatogenic defects.



    FULL STORY ==========================================================================
    A new gene that controls the completion of meiosis in spermatogenesis
    has been discovered by researchers from Kumamoto University. Until now,
    details of the mechanism that inactivates the expression of genes involved
    in the meiotic program during spermatogenesis had not been clarified. The researchers believe that this may lead to an advancement in reproductive medicine, like identifying causes for infertility from azoospermia or spermatogenic defects.


    ========================================================================== Meiosis is the special type of cell division that takes place in the
    ovaries and testes to produce eggs and sperm by reducing the number
    chromosomes to half the original. After meiosis is complete, DNA continues
    to be highly condensed and undergoes major morphological changes that are characteristic of spermiogenesis. This process inactivates the expression
    of many genes that were previously active in carrying out meiosis in spermiogenesis. However, the details of the mechanism that completes the meiotic program at the appropriate time are unknown, and although this
    is an important issue that is directly related to reproductive medicine,
    such as male infertility, it has remained an unresolved issue many years.

    Professor Ishiguro's group at Kumamoto University's Institute of
    Molecular Embryology and Genetics (IMEG) previously discovered MEIOSIN,
    a gene that switches on meiosis and causes hundreds of genes involved
    in sperm and egg formation to activate simultaneously. Among them, many
    genes have functions that are still not fully understood. In their work
    to ascertain these functions, the researchers selected the ZFP541 gene
    to analyze in detail.

    When the function of the ZFP541 gene in mice was eliminated using genome editing, male germ cells started meiosis but died in the process resulting
    in infertility since no sperm were produced. A detailed analysis of the
    testes of those mice revealed that the ZFP541 gene plays an essential
    role in the regulation of meiosis and is an important gene involved in
    sperm production.

    Furthermore, ZFP541 is expressed in late meiotic prophase and binds to the regulatory regions (called promoters) of many meiosis-related genes. It
    is known that acetylated histones are present in the regulatory region of promoters as a marker for sustained activation of gene expression. Through
    mass spectrometry analysis, researchers found that ZFP541 binds to an
    unknown protein called KCTD19 and an enzyme called HDAC1 that has been
    shown by previous studies to remove acetyl groups from histones. These
    results show that ZFP541 and HDAC1 together eliminate the histone acetyl
    group, inactivate the expression of meiosis-related genes, and complete meiosis.

    "This research is a follow-up to our discovery of MEIOSIN published in
    February of 2020 and reveals part of the function of a gene under the
    control of MEIOSIN whose function is still unknown," said Dr. Yuki Takada,
    who led the study.

    "Although these results were verified in mice, ZFP541 is also known to
    exist in humans. There are many cases of infertility in humans where
    the cause is unknown, but we expect that this result will contribute to
    the elucidation of the pathogenesis of infertility, especially those
    related to sperm dysplasia." The researchers also believe that their
    research can be applied to the development of infertility treatment
    technology. By elucidating the functions of other genes in the process
    of egg and sperm formation, they hope to make a significant contribution
    to reproductive medicine.

    ========================================================================== Story Source: Materials provided by Kumamoto_University. Note: Content
    may be edited for style and length.


    ========================================================================== Journal Reference:
    1. Yuki Horisawa-Takada, Chisato Kodera, Kazumasa Takemoto, Akihiko
    Sakashita, Kenichi Horisawa, Ryo Maeda, Ryuki Shimada, Shingo Usuki,
    Sayoko Fujimura, Naoki Tani, Kumi Matsuura, Tomohiko Akiyama,
    Atsushi Suzuki, Hitoshi Niwa, Makoto Tachibana, Takashi Ohba,
    Hidetaka Katabuchi, Satoshi H. Namekawa, Kimi Araki, Kei-Ichiro
    Ishiguro. Meiosis-specific ZFP541 repressor complex promotes
    developmental progression of meiotic prophase towards completion
    during mouse spermatogenesis. Nature Communications, 2021; 12 (1)
    DOI: 10.1038/s41467-021-23378-4 ==========================================================================

    Link to news story: https://www.sciencedaily.com/releases/2021/08/210824135347.htm

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