In a new study, researchers from the Lawrence Berkeley National Laboratory, the University of California at Berkeley, and the Albert Einstein College of Medicine provided evidence to prove that as an unusual part of DNA, heterochromatin utilization Liquid-liquid phase separation assembles a large portion of the genome into specific regions in the nucleus. Liquid-liquid phase separation is a well-known mechanism in physics, but its biological importance has only recently been revealed. These findings address a long-standing problem of how DNA functions are arranged spatially and temporally, including how genes are regulated to silence or express. The relevant research results were published online in the Nature Journal on June 21, 2017, and the paper titled "Phase separation drives heterochromatin domain formation".
According to Gary Karpen, senior author of the Department of Biosystems and Engineering at Lawrence Berkeley National Laboratory, "The importance of DNA sequences in health and disease has been clear for decades, but we only recently realized that DNA fragments are Assembly into different domains or compartments within the nucleus is critical to promoting different genomic functions."
The long fragment DNA in the heterochromatin contains a sequence that needs to be silenced in most cases so that the cell can function properly. Scientists once thought that this compression of DNA is a major mechanism controlling which enzymes and molecules are exposed to these sequences. It is inferred that the tighter the DNA strand is entangled, the harder it becomes to contact the internal genetic material.
In recent years, this machine preparation has been questioned because some large protein complexes have been found to be accessible to this heterochromatin domain, whereas smaller proteins are not accessible.
In a new study that used early Drosophila embryos and mouse cells as experimental subjects, the researchers observed two fluids in the nucleus that could not be mixed together: one liquid containing the expressed gene, and the other The liquid contains silent heterochromatin. They found that heterochromatin droplets fuse like two drops of oil surrounded by water.
In laboratory experiments, these researchers purified a major component of heterochromatin, heterochromatin protein 1a (HP1a), and observed that by forming droplets, this component was able to reproduce them. The situation observed in the nucleus.
Amy Strom, the first author of the paper and a graduate student at Karpen Labs, said, "We are excited about these findings because they explain a decade of secrets in this field. This is if this compression control is in contact with silent sequences, then How can other large proteins still be exposed to it? Chromatin assembly using phase separation methods that target proteins to one liquid or another is not based on size, but on other physical properties such as charge, Flexibility and interaction objects."
In another study titled "Liquid droplet formation by HP1α suggests a role for phase separation in heterochromatin", which was published in the journal Nature in the same period, researchers at the University of California, San Francisco confirmed that human HP1a protein has the same droplet properties. This suggests that similar principles apply to human heterochromatin.
It is interesting to note that this liquid-liquid phase separation is very sensitive to temperature changes, protein concentration and pH.
Strom said, "This is an elegant way for cells to manipulate gene expression in many sequences simultaneously."
Other cellular structures, including some of the cell structures involved in the disease, are also assembled by phase separation.
Karpen said, "The problem of phase separation is associated with diseases such as dementia and certain neurodegenerative diseases."
Karpen notes that as we get older, biological molecules lose their liquid state, become more rigid, and accumulate damage during this process. He pointed out that in diseases such as Alzheimer's disease and Huntington's disease, proteins are misfolded and aggregated, gradually losing their liquid state after a period of time and becoming more rigid.
Strom added, “If we can better understand what causes aggregation and how to increase its liquidity, then we may have a chance to fight these diseases.â€
This research is a major advance in understanding how DNA functions, and it may also help improve people's ability to manipulate genes.
"Gene therapy, or any therapy that relies on tight regulation of gene expression, may be improved by accurately targeting molecules to the appropriate location in the nucleus," Karpen said. "Targeting genes located in heterochromatin is very difficult, and This understanding of the nature of phase separation and liquid behavior may help to change this situation and allow us to manipulate one-third of the genome that was previously unmanageable."
Shanghai Chuangsai Technology has excellent performance, interleukin cytokines, fetal bovine serum, electrophoresis equipment scientific instruments, raw material drug standards, chemical reagents, cell culture consumables, Shanghai Chuangsai, mass products special promotions, welcome to inquire!
Joystar Electrical Appliances Manufacturing Co.,Ltd , https://www.cnjoystar.com