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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