Biologists unravel another mystery of what makes DNA go 'loopy'

By Carol Clark | eScienceCommons | March 26, 2018

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Interior of a cell showing the nucleus with the chromatin fiber (yellow) arranged in the three-dimensional space by loops formed by the CTCF protein (shown in pink). DNA is represented by thin blue lines on the chromatin. Graphic by Victor Corces.

Scientists discovered another key to how DNA forms loops and wraps inside the cell nucleus — a precise method of “packing” that may affect gene expression.

The journal Science published the research by biologists at Emory University, showing that a process known as hemimethylation plays a role in looping DNA in a specific way. The researchers also demonstrated that hemimethylation is maintained deliberately — not through random mistakes as previously thought — and is passed down through human cell generations.

“In order for a protein called CTCF to make loops in the DNA, we discovered that it needs to have hemimethylated DNA close by,” says Emory biologist Victor Corces, whose lab did the research. “Nobody had previously seen that hemimethylated DNA has a function.”

Chenhuan Xu, a post-doctoral fellow in the Corces lab, developed experimental methods for DNA methylome mapping to conduct the research for the Science paper.

Chromatin is made up of CTCF and other proteins, along with DNA and RNA. One role of chromatin is to fold and package DNA into more compact shapes. Growing evidence suggests that this folding process is not just important to fit DNA into a cell nucleus — it also plays a role in whether genes are expressed normally or malfunction.

The Corces lab specializes in epigenetics: The study of heritable changes in gene function — including chromatin folding — that do not involve changes in the DNA sequence.

DNA methylation, for example, can modify the activity of DNA by adding methyl groups to both strands of the double helix at the site of particular base pairs. The process can be reversed through demethylation.

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