Heterozygous loss of the gene encoding the methyl-CpG-binding protein Zbtb38 leads to early embryonic death due to the deletion of the Nanog and Sox2 transcription factors.

DNA methylation is a major epigenetic modification critical for mammalian development. For example, DNA methylation is central to inexhaustible biological processes such as gene regulation and cell fate. In mammals, DNA methyltransferases are required by blastocysts to restore global DNA methylation patterns after implantation. This is necessary for the transmission of epigenetic information to the next generation. On the other hand, the role of methyl-CpG-binding proteins (MBPs), which bind methylated CpG as part of DNA methylation processes, is still unclear. However, a previous study by researchers at the Nara Institute of Science and Technology (NAIST), Japan, made this clear; Zbtb38, also known as CIBZ, is a type of zinc finger MBP that is required for the growth of mouse embryonic stem (ES) cells. They also demonstrated that Zbtb38 promotes the expression Nanog, which is fundamental to the growth of ES cells. However, what Zbtb38 does in real life remains a mystery.

In another quest to unravel this mystery, the same NAIST scientists, led by Eishou Matsuda, used Cre-loxP technology to conditionally Zbtb38 knockout mice. Their groundbreaking study found that only one Zbtb38 deletion of germline alleles resulted in reduced growth of epiblast cells and increased apoptosis shortly after implantation, leading to early embryonic death. Nanog, Sox2 and the genes that control epiblast growth and differentiation cease to function when Zbtb38 lost in heterozygous embryos.

“Our results show that germline loss Zbtb38 one allele reduces epiblast cell proliferation and increases apoptosis shortly after implantation, resulting in early embryonic lethality. heterozygous Zbtb38 deficiency reduces expression Nanog, Sox2 and genes involved in the proliferation, differentiation and viability of epiblast cells. This finding shows that the methyl-CpG binding protein plays a role in the control of the embryonic phenotype,” says Matsuda.

“For the first time, we have demonstrated an association with the embryonic function of a protein known to bind methyl-CpG,” says study co-author Yasumasa Ishida. “This opens up a huge opportunity for further research to find out how Zbtb38 functions during embryogenesis. Further research is needed to elucidate specific molecular mechanisms. Zbtb38 is found in all tissues and is associated with growth, cancer, neurodegenerative diseases, rheumatoid arthritis, etc. Thus, the creation and analysis of mice with tissue-specific Cre-mediated knockout will help us understand the physiological functions of Zbtb38 and Zbtb38 related diseases., concludes Matsuda.

The results of this work will be of interest to developmental biologists as they highlight the epigenetic importance of DNA methylation in early pregnancy.

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Link to the journal:

  1. Miki Nishio, Takuya Matsuura, Shunya Hibi, Shiomi Ohta, Chio Oka, Noriaki Sasai, Yasumasa Ishida, Eishou Matsuda. Heterozygous loss of Zbtb38 leads to early embryonic lethality due to suppression of Nanog and Sox2 expression.. cell spread, 2022; DO I: 10.1111/cpr.13215

Quote this page:

Nara Institute of Science and Technology. Single allele deletion in the gene encoding Zbtb38 results in early embryonic death: Heterozygous loss of the gene encoding the Zbtb38 methyl-CpG-binding protein results in early embryonic death through the deletion of the Nanog and Sox2 transcription factors. » . , April 18, 2022 .

Nara Institute of Science and Technology. (2022, April 18). Deletion of one allele in the gene encoding Zbtb38 leads to early embryonic death: heterozygous loss of the gene encoding the methyl-CpG-binding protein Zbtb38 leads to early embryonic death due to the deletion of the Nanog and Sox2 transcription factors. ScienceDaily. Retrieved April 19, 2022 from www.sciencedaily.com/releases/2022/04/220418094008.htm.

Nara Institute of Science and Technology. Single allele deletion in the gene encoding Zbtb38 results in early embryonic death: Heterozygous loss of the gene encoding the Zbtb38 methyl-CpG-binding protein results in early embryonic death through the deletion of the Nanog and Sox2 transcription factors. » . www.sciencedaily.com/releases/2022/04/220418094008.htm (accessed 19 April 2022).

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