New findings highlight how the process of ‘resetting’ takes place in a fertilized egg cell, enabling the development of a fresh embryo. Researchers found that a group of genes known as OBOX1-8 are crucial for activating the embryo’s unique genetic program. This important insight, which enhances our understanding of zygote genome activation, was gleaned from studies on mice and could influence how embryonic stem cells are reprogrammed.
A team of researchers from the United States and China has shed light on the process by which a fertilized egg cell, also referred to as a zygote, initiates a ‘reset’. This crucial process allows the embryo to develop according to its own unique genetic program. Their findings were recently published in the scientific journal, Nature.
“The genome of a newly fertilized egg cell is initially inactive and needs to be awakened. This process is known as zygote genome activation,” explained Richard Schultz, a research professor at the University of California, Davis, School of Veterinary Medicine and one of the paper’s authors.
To transform into an embryo, the egg cell must discard its own identity and begin creating new elements. “We have now begun to understand the initial steps of this transformative process,” said Schultz.
To initiate the reset or awakening process, the embryo must transcribe genes from its DNA into messenger RNA, which is subsequently translated into proteins. The first genes to be transcribed then stimulate other genes, thereby initiating the genetic program that allows the embryo to develop into a complete organism. Until now, the exact identity of these initial master-regulator genes remained unknown.
Schultz explained the crucial role of RNA polymerase II (Pol II), the enzyme responsible for transcribing DNA into RNA. However, this enzyme cannot function in isolation. It needs the support of other genes, called transcription factors, to guide it in transcribing the correct genes at the right time.
In the early 2000s, Schultz hypothesized that these initial transcription factors would be found among dormant maternal messenger RNAs present in the egg cell. These dormant RNAs, unique to oocytes, are translated into proteins only as the oocyte matures into an egg, at which point they carry out their function. Schultz proposed that the information needed for zygote genome activation would be encoded in one such dormant maternal messenger RNA, which would serve as the master transcription factor.
The OBOX1-8 gene family emerged as potential candidates during Schultz’s work with Paula Stein at the University of Pennsylvania, and now at the National Institute of Environmental Health Sciences. The team collaborated with Wei Xie at Tsinghua University, Beijing, to further narrow down these candidates.
In experiments involving lab mice, Xie’s team managed to disable all the likely candidate genes and then systematically restore the OBOX genes to identify the ones critical for zygote genome activation. Without these genes, embryo development halted at the two to four-cell stage.
Interestingly, the researchers found that the function of OBOX genes was highly redundant, meaning that if one was knocked out, another could take its place. This redundancy is believed to have evolved due to the significance of the transition process, Schultz suggested. Additionally, the OBOX genes were found to aid Pol II in locating the correct genes to initiate zygote genome activation.
In mice, genome activation occurs at the two-cell stage, while in human embryos, it takes place a bit later, after the embryo has undergone a few rounds of cell division to form eight cells. An intriguing question is whether this process is consistent across different species and if similar OBOX-like genes are involved in genome activation in humans. Furthermore, these findings could have implications for how embryonic stem cells are reprogrammed, allowing them to develop into any body tissue.
The research was funded by the National Natural Science Foundation of China, the National Key Research and Development Program of China, the National Institutes of Health, and the National Institute of Environmental Health Sciences.
Reference: “OBOX regulates murine zygotic genome activation and early development” by Shuyan Ji, Fengling Chen, Paula Stein, Jiacheng Wang, Ziming Zhou, Lijuan Wang, Qing Zhao, Zili Lin, Bofeng Liu, Kai Xu, Fangnong Lai, Zhuqing Xiong, Xiaoyu Hu, Tianxiang Kong, Feng Kong, Bo Huang, Qiujun Wang, Qianhua Xu, Qiang Fan, Ling Liu, Carmen J. Williams, Richard M. Schultz and Wei Xiong, 17 July 2023, Nature. DOI: 10.1038/s41586-023-06428-3
Table of Contents
Frequently Asked Questions (FAQs) about Embryo Genome Activation
What are OBOX1-8 genes and why are they significant in the development of a new embryo?
OBOX1-8 genes are a group of genes that are crucial for initiating the genetic program of a new embryo. They play a critical role in the ‘resetting’ process of a fertilized egg cell or a zygote, enabling it to develop according to its own genetic program.
What is the process of zygote genome activation?
Zygote genome activation is the process where a fertilized egg cell’s inactive genome is ‘awakened’ to allow the embryo to develop. The embryo begins to transcribe genes from its DNA into messenger RNA, which then gets translated into proteins. The first genes to be transcribed activate other genes, setting the genetic program in motion that allows the embryo to develop into a complete organism.
How was this discovery made?
The discovery was made through a collaborative study conducted by researchers in the United States and China. By working with lab mice, the researchers disabled potential candidate genes and systematically restored the OBOX genes to identify the ones crucial for zygote genome activation.
What are the implications of this research?
This research offers significant insights into the early stages of embryonic development, potentially informing how embryonic stem cells can be reprogrammed to develop into any body tissue. It also raises questions about the potential similarities in genome activation across different species.
Who funded this research?
The research was funded by the National Natural Science Foundation of China, the National Key Research and Development Program of China, the National Institutes of Health, and the National Institute of Environmental Health Sciences.
More about Embryo Genome Activation
- Study Published in Nature
- University of California, Davis, School of Veterinary Medicine
- National Institute of Environmental Health Sciences
- National Natural Science Foundation of China
- National Institutes of Health
- Tsinghua University, Beijing
