Release date: 2018-03-20
We know that precise DNA packaging compression affects gene expression. Do you know how DNA is twisted into a circle?
The loop formed by the CTCF protein (pink), the chromatin fibers (yellow) and the DNA on the chromatin (blue lines) are arranged.
A biologist at Emory University recently published an article in Science, reporting on the specific function of cells "hemimethylation." This article overturns the previous speculation theory of hemimethylation, and proves that the process is not a "random error" of adding leaves and leaves, but "deliberate" that human cells have passed down from generation to generation.
"The protein that loops DNA into loops is called CTCF. Through this study we found that CTCF proteins require hemimethylated DNA," said Professor Victor Corces, a subject leader. “No one has reported that hemimethylated DNA has this function.â€
DNA methylation alters DNA activity by adding a methyl group to a particular base pair of both strands of the DNA double helix, which effect can be reversed by demethylation.
When the cell divides, the DNA also replicates. Before the DNA is copied, the double strand needs to be unfolded, and the daughter strand is a replica of the parent strand. "It's important to maintain the same DNA methylation status during cell division," Corces said. "Changes in methylation patterns have been shown to be associated with diseases such as cancer."
Hemimethylation is one in which one chain is added with one methyl group and the other chain is not added. When some researchers observed the phenomenon of hemimethylation, they speculated that it might be because the time point of observation was after cell division and before the sub-chain was completely replicated. Another theory is that hemimethylation is a random error in the methylation process.
However, Chenhuan Xu, a postdoctoral researcher at Corces Labs, does not think so.
They developed a new experimental method for DNA methylation mapping. In this "Science" article, researchers have observed the real-time dynamics of DNA hemimethylation in the whole process before, during and after human cell replication.
"If the parental DNA is hemimethylated, the progeny DNA is also hemimethylated at the same genomic location," Corces said. "This process is not random, but continues from the next generation to the next generation."
The researchers found that hemimethylation only occurs at the binding site of CTCF, the major protein involved in DNA loop formation.
CTCF is one of the components of chromatin, which functions to fold and compress DNA into a more dense shape. There is increasing evidence that the folding process of DNA is not only to adapt DNA to a small space within the nucleus, but also to one of the reasons that affect the normal or dysregulated expression of genes.
Scientists also specialize in epigenetics to study heritable changes in genetic function, including chromatin folding, which does not involve changes in DNA sequence.
"If artificially removes the hemimethylation, the CTCF will no longer participate in the ring," Corces said. "The effect of hemimethylation seems to make CTCF loop."
The researchers observed that when CTCF made a DNA loop, it binds to the forefront and leads the DNA sequence forward.
"Past studies have shown that certain diseases are associated with CTCF-associated disorders, such as mutations in the CTCF protein itself, or mutations in DNA sequences that bind to it," Corces said. “Today, we pull the problem back to the DNA loop and chromatin three-dimensional organization and how they affect gene expression.â€
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