X chromosomes are one of the two sex chromosomes in mammals. In females, there are two X chromosomes, while males have one X chromosome and one Y chromosome. To balance gene expression between males and females, one of the X chromosomes in females is randomly inactivated during development, a process known as X-inactivation.
Exactly how X chromosomes fold and deactivate has been a mystery for many years. To address this question, the OIST researchers used a combination of experimental and computational techniques, including supercomputer simulations and advanced imaging technologies.
"We used supercomputer simulations to model the folding of the X chromosomes at a very high level of detail. We found that the X chromosomes fold into a specific 3D structure that brings together the genes that need to be silenced," said Dr. Ana Pombo, senior author of the study and head of the Gene Expression Regulation Unit at OIST.
The researchers also found that the folding of the X chromosomes is controlled by a protein called CTCF. CTCF acts as a boundary element, preventing the genes on the X chromosomes from interacting with genes on other chromosomes.
"Our study provides new insights into the mechanisms of X-inactivation and gene regulation. It also highlights the power of supercomputers for studying complex biological processes," said Dr. Pombo.
The findings could have implications for understanding developmental disorders and sex chromosome aneuploidies. For example, mutations in the CTCF gene have been linked to several developmental disorders, including Cornelia de Lange syndrome. Understanding the role of CTCF in X-inactivation could help researchers better understand these disorders and develop new treatments.
This research was supported by the Okinawa Institute of Science and Technology Graduate University, the Japan Society for the Promotion of Science, and the European Research Council.
