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Scientists unveil the most precise 3D human genome model yet


Ever wonder how a 6-foot-long strand of DNA can fit in a cell that’s smaller than the head of a pin?
 
Researchers from the Baylor College of Medicine have just created the most precise 3D model yet of how the genome organizes itself within the cell and how this affects the expression of genes.
 
It’s long been known that the genome “folds” itself in a way that allows all that genetic information to fit inside a cell and still allow that information to be accessed when needed. Using molecular probes, they were able to generate a 3D model of the genome, showing how genome is compartmentalized and how this organization affects function.
 
Suhas Rao and colleagues found that the human genome naturally forms into DNA loops, which are 200,000 base pair long strands of DNA containing genes and regulatory factors, organized in a loop (duh), and usually function as a unit. 
 
 
These loops form when a protein called CTCF finds a specific motif or DNA sequence and binds to it. Two motifs bind to the protein, forming a loop. These loops eventually group together into domain that are organized or “folded” according to function. The domains are then grouped together into subcompartments organized around histones.
 
Only 2% of our entire genome is composed of genes, the rest are specific DNA sequences that affect the expression of these genes. And like a spool of thread, where these genes and regulatory factors are located would determine how often these genes are expressed or how easily they can be altered or damaged. They discovered that different types of cells, though they contain the same genome, fold their DNA differently. This allows for certain genes to be expressed while some are repressed, which helps explain how a wide variety of cells with varying functions can arise from a single genome.
 
Genetics and Disease
 
Not only does this model help explain the varying gene expression, knowing how DNA loops are formed and how they work could help us better understand the development of human disease, specifically cancer.
 
According to Dr. Barry Star of the Tech Museum & Stanford University, DNA loops could help explain how genetic regulation of cell replication could go awry and eventually lead to cancer.
 
In a particular DNA loop, for example, the genes and factors that regulate the expression of genes with that loop maybe located within the loop or outside the loop, depending on how often the gene needs to be expressed.
 
To best understand how this works would to imagine running a piece of string through a bead. If there are no loops or tangles along the string, the string would be able to pass through the bead easily. Once the bead encounters a tangle, you would need to unwind the string in order to help it pass through.
 
In a DNA loop, sometimes the “tangles” or loops are necessary in order to create a barrier between factors that promote or enhance the expression of certain genes. Genes that promote cell replication, for example, should only be activated during growth or tissues repair. But when a mutation or drug disrupts the loop, causing it to unravel for example, cell replication is no longer regulated, eventually forming cancer.
 
DNA = Origami?
 
In their YouTube video, the researchers explain that genome folding is a lot like origami. Origami only has two basic folds, the mountain fold and the valley folds. By using these two basic folds in different ways, you can create numerous possibilities. It’s the same thing with our genome. Folding drives function. We’re mostly the same, the differences we see in each other are just variations of a few basic folds. — TJD, GMA News
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