The cell stores all of its genetic material in its nucleus in the form of chromosomes, but there’s more hidden away in there. The nucleus also contains small bodies referred to as nucleoli, which are clusters of proteins or RNA that aid in the creation of ribosomes.
Through computer simulations, MIT chemists have now discovered how these bodies interact with chromosomes within the nucleus. They also discovered how those interactions allow the nucleoli to function as stable droplets inside the nucleus.
Their findings also suggest that chromatin-nuclear-body interactions cause the genome to adopt the shape of a gel, which assists in promoting stabile interactions between the genome and transcription machineries. These interactions help control the expression of genes.
This model has inspired us we think that the genome may have gel-like properties that could aid in the process of coding important contacts and translate them into useful outputs.
Bin Zhang, the Pfizer-Laubach Career Development Associate Professor of Chemistry at MIT and associate member of the Broad Institute of Harvard and MIT and senior author of the study
The paper was written by Yifeng Qi, a graduate student at MIT. It is published in Nature Communications.
Much of Zhang’s work focuses on modeling the three-dimensional structure of the genome and studying how that structure affects gene regulation.
He wanted to expand his modeling to include nucleoli in his new study. These tiny bodies, which are broken down during cell division and then re-formed in the process, are made up of more than 1000 molecules of RNA, as well as proteins. One of the primary roles of the nucleoli is to produce ribosomal RNA, a component of ribosomes.
Recent research suggests that nucleoli could exist in multiple liquid droplets. This was puzzling because under normal conditions, many droplets should eventually fuse together to form one big droplet to reduce the surface tension of the system, Zhang says.
He adds, “That’s where it gets fascinating, because somehow those multiple droplets can stay stable over an entire cell cycle over approximately 24 hours.”
Zhang and Qi utilized molecular dynamics simulation to study this phenomenon. This technique can simulate how a molecular system alters over the course of time. The simulation begins with nucleoli’s proteins and RNA being randomly distributed throughout the nucleus. The simulation then tracks the gradual formation of these proteins into small droplets.
In their simulation, the researchers included chromatin, the chemical that makes up chromosomes and contains DNA as well as proteins. The MIT team used data from previous research to analyze the structure of chromosomes as well as calculated the interaction energy of individual chromosomes. This allowed them to construct realistic representations of 3D genomes.
Using this model, the researchers were able to observe how nucleoli droplets form. They found that the nucleolar components could be modeled by themselves without chromatin. They would then combine to form a single droplet. However when chromatin was incorporated into the model, they found that the nucleoli formed multiple droplets, as they do in living cells.
Researchers also discovered why this occurs. The nucleoli droplets are tethered to certain areas of the chromatin. Once that happens the drag created by the chromatin stops nucleoli from joining to each other.
Zhang says that these forces “essentially arrest the system into tiny droplets and stop the fusion of these droplets.” “Our study is the first to highlight the importance of this chromatin network that could significantly slow down the fusion and arrest the system in its droplet state.”
The nucleoli aren’t the only tiny structures that are found in the nucleus . other examples include nuclear speckles as well as the nuclear lamina. It is an envelope that surrounds the genome and is able to bind to chromatin. Zhang’s group is now studying the roles of these nuclear structures, and their preliminary findings suggest that they help to give the genome more gel-like properties, Zhang says.
“The coupling we have observed between the nuclear bodies, chromatin, and nucleoli isn’t just for the nucleoli. It is common to other nuclear bodies too,” he says. “This nuclear body concentration will fundamentally alter the dynamics of genome organisation and will very likely change the genome from liquid to gel.”
This gel-like state would make it easier for different regions of chromatin to interact with one more easily than if the structure was in a liquid state, he says. Because genes are often controlled from stretches of chromatin that are physically separated It is crucial to ensure that interactions remain stable between distant areas of the genome.
The research was supported by the National Institutes of Health and the Gordon and Betty Moore Foundation.
Qi, Y & Zhang, B., (2021) Chromatin network retards nucleoli coalescence. Nature Communications. doi.org/10.1038/s41467-021-27123-9.
Content Source: https://www.news-medical.net/news/20211125/MIT-scientists-discover-how-molecular-clusters-interact-with-chromosomes-in-the-nucleus.aspx