Spatially coordinated heterochromatinization of long synaptic genes in fragile X syndrome. (https://pubmed.ncbi.nlm.nih.gov/38134876/)

These scientists wanted to understand why some people have a condition called fragile X syndrome (FXS). In FXS, there is a problem with a part of the DNA called CGG, which makes a protein called FMR1. The scientists studied cells from patients with FXS and found that there were big areas on the DNA that had a chemical mark called H3K9me3. These areas were found on both the X chromosome and other chromosomes in the cells.

The scientists also discovered that these H3K9me3 areas were connected to each other and caused the DNA to fold in a way that was not normal. This folding affected how genes worked and caused some of them to be turned off. The H3K9me3 areas also had genes that were important for communication between brain cells and were more likely to have problems during cell division.

To test their findings, the scientists used a tool called CRISPR to change the CGG in the DNA of the cells from patients with FXS. When they changed the CGG to a shorter length, the H3K9me3 areas disappeared and the DNA folded correctly again. The genes started working normally and the cells became healthier.

The scientists also found that H3K9me3 areas could appear in cells that were not from patients with FXS, but only if there were other problems with the DNA. This suggests that these H3K9me3 areas are important for understanding not only FXS but also other conditions related to problems in the DNA.

In summary, the scientists discovered that in fragile X syndrome, certain parts of the DNA have a mark called H3K9me3, which causes the DNA to fold incorrectly and turns off important genes. By using a tool called CRISPR, they were able to fix this problem and make the DNA work normally again. They also found that this H3K9me3 mark can appear in other conditions if there are other problems with the DNA.

Malachowski T., Chandradoss KR., Boya R., Zhou L., Cook AL., Su C., Pham K., Haws SA., Kim JH., Ryu HS., Ge C., Luppino JM., Nguyen SC., Titus KR., Gong W., Wallace O., Joyce EF., Wu H., Rojas LA., Phillips-Cremins JE. Spatially coordinated heterochromatinization of long synaptic genes in fragile X syndrome. Cell. 2023 Dec 21;186(26):5840-5858.e36. doi: 10.1016/j.cell.2023.11.019.