Understanding the mechanisms that control the expression of genes linked to meiosis – sciencedaily
A new gene that controls the completion of meiosis in spermatogenesis has been discovered by researchers at Kumamoto University. Until now, details of the mechanism that inactivates the expression of genes involved in the meiotic program during spermatogenesis have not been clarified. Researchers believe this could lead to advances in reproductive medicine, such as identifying the causes of 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 of chromosomes to half of the original. After meiosis is terminated, DNA continues to be highly condensed and undergo 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 directly related to reproductive medicine, such as male infertility, it has remained an issue. unresolved for many years.
Professor Ishiguro’s group at the Institute of Molecular Embryology and Genetics (IMEG) at Kumamoto University previously discovered MEIOSIN, a gene that activates meiosis and causes the simultaneous activation of hundreds of genes involved in the formation sperm and ova. Among them, many genes have functions that are still poorly understood. In their work to verify these functions, the researchers selected the ZFP541 gene to be analyzed in detail.
When the function of the ZFP541 gene in mice was eliminated using genome editing, the male germ cells started meiosis but died in the process, resulting in infertility because no sperm were produced. Detailed analysis of the testes of these mice revealed that the ZFP541 gene plays an essential role in the regulation of meiosis and is an important gene involved in sperm production.
In addition, ZFP541 is expressed in late meiotic prophase and binds to 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, the researchers found that ZFP541 binds to an unknown protein called KCTD19 and an enzyme called HDAC1 which, according to previous studies, removes acetyl groups from histones. These results show that ZFP541 and HDAC1 together eliminate the acetylated histone group, inactivate the expression of genes related to meiosis and complement meiosis.
“This research follows our discovery of MEIOSIN published in February 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 this to occur. result contributes 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.
Source of the story: