New findings from RIKEN research team have highlighted the importance of two protein complexes, PRC1 and PRC2, in X-chromosome inactivation, a critical process in female mammals that, when malfunctioning, could potentially trigger cancers.
In female mammals, two protein complexes assume distinct yet crucial roles in inactivating one of the two X chromosomes.
The study by RIKEN researchers has shed light on the function of two protein complexes in the mysterious process of silencing one X chromosome in female mammals. This discovery could aid scientists in understanding how certain types of cancer develop in women.
While males carry one X and one Y chromosome, females possess two X chromosomes. This additional X chromosome usually offers females more protection against genetic disorders and cancers in comparison to males.
During development, females undergo X-chromosome inactivation, a mechanism that switches off one of the X chromosomes. If this process is disrupted, women may encounter serious health issues like breast cancer. A better grasp of the X-chromosome inactivation process could facilitate prevention or treatment of these kinds of tumor-inducing events in humans.
In an experiment using mouse embryos, Haruhiko Koseki’s team from the RIKEN Center for Integrative Medical Sciences (IMS) demonstrated the unique roles of the polycomb repressive complex 1 (PRC1) and PRC2 in maintaining one X chromosome dormant during the embryonic development.
Figure 1: A depiction of two X chromosomes highlighting the 23rd female chromosome pair. The study by RIKEN researchers uncovers how two protein complexes deactivate one X chromosome in female mammals.
Interestingly, the study found that only tissues supporting embryonic development depend on PRC1 and PRC2 to sustain gene silencing on the inactive X chromosome. Embryonic tissues themselves can maintain this chromosome dormant without these epigenetic regulators, indicating a different molecular machinery at work.
“This research underlines distinct characteristics of two major tissue types in developing embryos,” notes Osamu Masui, a member of the IMS team.
By examining genetically engineered mice lacking either of the protein complexes, the researchers pinpointed how PRC1 and PRC2 alter DNA coiling in different ways, silencing a unique group of genes on the inactive X chromosome.
While both complexes are vital for proper X-chromosome inactivation in tissues that later form organs like the placenta, they aren’t necessary in the embryo tissue itself.
“This research robustly shows that both PRC1 and PRC2 independently gather on the inactive X chromosome and differentially maintain silencing of X-linked genes,” Masui explains. “These findings could enhance our understanding of how female-specific tumors develop.”
The team is now working to unearth the molecular mechanisms that enable embryonic tissues to stringently control X-chromosome inactivation. “These studies should bolster our foundational knowledge of gene regulation within the genome,” adds Masui.
Citation: “Polycomb repressive complexes 1 and 2 are each essential for maintenance of X inactivation in extra-embryonic lineages” by Osamu Masui, Catherine Corbel, Koji Nagao, Takaho A. Endo, Fuyuko Kezuka, Patricia Diabangouaya, Manabu Nakayama, Mami Kumon, Yoko Koseki, Chikashi Obuse, Haruhiko Koseki and Edith Heard, 12 January 2023, Nature Cell Biology.
DOI: 10.1038/s41556-022-01047-y
Table of Contents
Frequently Asked Questions (FAQs) about X-chromosome inactivation
What are the protein complexes involved in X-chromosome inactivation?
The protein complexes involved in X-chromosome inactivation are Polycomb Repressive Complex 1 (PRC1) and Polycomb Repressive Complex 2 (PRC2).
What is the significance of these protein complexes in female mammals?
These protein complexes play vital roles in silencing one of the two X chromosomes in female mammals. This process is crucial for maintaining genetic balance and, when disrupted, could lead to cancers.
How are PRC1 and PRC2 involved in the process of X-chromosome inactivation?
In the process of X-chromosome inactivation, PRC1 and PRC2 gather on the inactive X chromosome and maintain the silencing of X-linked genes. They alter the DNA coiling in unique ways, each silencing a specific set of genes.
What does the study’s finding mean for understanding and combating female-specific cancers?
This research enhances our understanding of the mechanisms underlying X-chromosome inactivation. By doing so, it provides valuable insights into the development of female-specific cancers, potentially aiding in the prevention or treatment of such cancers.
What are the next steps in this line of research?
The research team is now working to uncover the molecular mechanisms that allow embryonic tissues to maintain X-chromosome inactivation strictly. This exploration should contribute to our fundamental understanding of gene regulation within the genome.
More about X-chromosome inactivation
- RIKEN Center for Integrative Medical Sciences
- Understanding X-chromosome Inactivation
- Polycomb Repressive Complexes and Cancer
- Understanding Gene Silencing
- Female-Specific Cancers: Overview
5 comments
fascinating research, it’s amazing how the tiniest of things in our bodies can have such huge impacts! keep going scientists!
Everytime I read something like this I’m reminded how awesome science is! great job to these folks at RIKEN for their hard work.
Absolutely mind-blowing research! I mean, who’d’ve thought proteins could play such a big part in stopping cancer! Keep up the great work RIKEN team!
Incredible stuff…it’s like every day we’re learning something new that could literally save lives. imagine what we could do in the next decade!
im no scientist but this seems like a major breakthrough. Why ain’t we funding this more??? lives could be saved, people!!