In a paper, researchers at the University of Washington School of Medicine in Seattle describe this finding.
According to Shiri Levy, a postdoctoral fellow at the UW Institute for Stem Cell and Regenerative Medicine (ISCRM), the approach will allow researchers to understand the role individual genes play in normal cell growth and development, as well as in other diseases such as cancer.
Levy believes that through this approach, we can easily upregulate specific genes in order to affect cell activity without permanently changing the genome and cause unexpected errors.
Hannele Ruohola-Baker, an ISCRM professor, led the project. Under the supervision ofDavid Baker, the AI-designed protein, the UW Medicine Institute for Protein Design (IPD) was developed under the direction of Dan Baker, a biochemistry professor and head of the Institute of Technology.
The new technique increases gene activity without altering the DNA sequence of the genome. These changes are aimed at structuring genes in our chromosomes, which are called epigenetic. These changes are not only in, but on the other hand, but also on the other hand, because they are called epigenetic. The chemical changes that regulate gene activity are called epigenetic markers.
Scientists are particularly interested in epigenetic modifications because they do not only affect gene activity in normal cell function, but epigenetic markers accumulate with time, contribute to ageing, and they may affect future generations as we can transfer them to our children.
Levy and her colleagues focused on a complex of proteins called PRC2, which silences genes by attaching a small chemical, called a methyl group, to a protein that contains genes called histones. These methyl groups must be refreshed so that if PRC2 is blocked the genes it has silenced. it may be reawakened.
PRC2 is active throughout development, but it plays a significant role during development during embryonic cells separating into different molecules that will form the tissues and organs of the growing embryo. However, chemicals are required to prevent PRC2 from being blocked, causing PRC2 to be altered if only one gene at a time.
To do this, David Baker and his colleagues use AI to create a protein that would bind to PRC2 and block a protein the PRC2 uses to modify the histones. Later, Ruohola-Baker and Levy combined this designed protein with a disabled version of a Cas9.
Cas9 is the protein used in the gene editing process called CRISPR. This process allows scientists to obtain Cas9 to a specific address-tag RNA, thus the ability to cut and splice genes at specific locations remains active. In this experiment, however, the Cas9 function as a vehicle to deliver cargo to a specific location is not compromised. According to Levy, the guide RNA is like a passenger.
Levy and her colleagues demonstrate that by using this technique, they were able to block PRC2 and selectively turn on four different genes. They were also able to demonstrate that by simply turning on two genes, they could transdifferentiate induced pluripotent stem cells.
Levy said this technique allows us to avoid bombarding cells with various growth factors, gene activators and repressors to make them differentiated.
Instead, we may target specific areas on the gene transcription promoters area, lift those marks, and let the cell do the rest in an organic and holistic manner.
Finally, the researchers were able to demonstrate how the technique can be used to determine the location of specific PRC2-controlled regulatory regions from which individual genes are activated. In this case, they identified a promoter region called a TATA box for a gene calledTBX18. Although current reasoning is that these promotor regions are close to the gene, they discovered for this gene the promoter region was more than 500 base pairs away.
According to Ruohola-Baker, TATA boxes are scattered throughout the genome, and current research in biology shows that the important TATA boxes are very close to the gene transcription site, and others do not. This tool is able to find the critical PRC2 dependent elements, in this case TATA boxes that are significant.
In accordance with these two advances, AI-designed proteins and CRISPR technology, we can now identify the exact epigenetic markings that are important for gene expression, learn the rules, and leverage them to monitor cell function, drive cell differentiation, and develop 21stcentury therapies.