A single allele deletion in gene encoding Zbtb38 leads to early embryonic death

A single allele deletion in gene encoding Zbtb38 leads to early embryonic death

Heterozygous loss of Zbtb38 (Zbtb38 +/-) reduced epiblast cell proliferation and increased apoptosis shortly after implantation (E4.5 ~), leading to early embryonic mortality. Nanog and Sox2 expressions were reduced in the Zbtb38 +/- embryos. ICM: internal cell mass. Credit: Eishou Matsuda

DNA methylation is a major epigenetic modification that is essential for mammalian development. For example, DNA methylation is central to inexhaustible biological processes, such as gene regulation and cell fate decisions. In mammals, DNA methyltransferases are the key for blastocysts to re-establish global DNA methylation patterns during implantation. This is essential for passing on epigenetic information to the next generation.

On the other hand, the role of methyl CpG binding proteins (MBPs) that bind methylated CpG as part of the DNA methylation processes is still unclear. However, a previous study conducted by researchers at the Nara Institute of Science and Technology (NAIST), Japan, clarified that; Zbtb38, also known as CIBZ, is a zinc finger type MBP that is essential for the growth of mouse embryonic stem cells (ES). They further showed that Zbtb38 facilitates the expression of Nanog, which is fundamental for the growth of ES cells. What Zbtb38 does in real life, however, is still a mystery.

In a further quest to solve this mystery, the same scientists at NAIST, led by Eishou Matsuda, used Cre-loxP technology to make conditional Zbtb38 knockout mice. Their research revealed that a single Zbtb38 allele deletion in the germ line led to a decrease in epiblast cell growth and an increase in apoptosis shortly after implantation, leading to early embryonic death. Nanog, Sox2, and genes that control epiblast growth and differentiation became dysfunctional as Zbtb38 was lost in heterozygous embryos.

“Our results indicate that germline loss of the Zbtb38 single allele reduces epiblast cell proliferation and increases apoptosis shortly after implantation, resulting in early embryonic mortality. Heterozygous Zbtb38 deficiency reduced the expression of Nanog, Sox2 and genes involved in epiblast proliferation and differentiation of cells. findings show that a methyl-CpG-binding protein has a role in controlling embryonic phenotype, “explains Matsuda.

“For the first time, we showed a link to an embryonic function of a protein that has long been known to bind methyl-CpG,” says co-author Yasumasa Ishida. “This provides a huge opportunity for further research to find out how Zbtb38 works during embryogenesis. More research needs to be done to elucidate the specific molecular mechanisms. Zbtb38 is found in all tissues and is associated with height, cancers, neurodegenerative diseases and rheumatoid arthritis, etc. Thus, the creation and analysis of tissue-specific Cre-mediated knockout mice will help us understand the physiological functions of Zbtb38 and Zbtb38-associated diseases, ā€¯Matsuda concludes.

The results of this work will interest developmental biologists as it underscores the epigenetic significance of DNA methylation in the early stages of pregnancy.

The research was published in Cell proliferation.

‘Roadmap’ tracks paths for embryo development

More information:
Miki Nishio et al., Heterozygous loss of Zbtb38 leads to early embryonic mortality via suppression of Nanog and Sox2 expression, Cell proliferation (2022). DOI: 10.1111 / cpr.13215

Provided by the Nara Institute of Science and Technology

Citation: A single allele deletion in gene encoding Zbtb38 leads to early embryonic death (2022, April 18) Retrieved April 18, 2022 from https://phys.org/news/2022-04-allele-deletion-gene -encoding-zbtb38.html

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