Salk Institute scientists decode DNA’s 3D shape

DNA is compressed in the nucleus in a disorderly way that allows flexibility in how genes are turned on and off, according to a study by Salk Institute scientists.

This discovery was made with a new imaging technology invented by Salk researchers led by Clodagh O’Shea. Published in Science, the study is available at j.mp/salkdna. O’Shea was senior author; the first author was Horng Ou, a researcher in her lab.

Understanding DNA’s 3D structure is expected to yield a better understanding of how defects in that structure relate to senescence and diseases, according to a perspective piece published along with the study.

In the nucleus, DNA is bound to proteins to make a complex called chromatin, which in turn forms chromosomes. The degree of compression is extreme. Stretched out to form a line, the DNA in a single cell would extend about one meter, or about six feet. It must all fit into a nucleus of about 10 millionths of a meter.

“What that means is that not all your DNA is accessible,” O’Shea said. “So even though the same DNA sequence is in every cell in your body, its structure in any cell nucleus can be different, which determines whether those DNA sequences can be accessed and used.”

“The fundamental question then is, well what’s the structure of DNA in the nucleus,” she said.

Existing models envision DNA as being grouped in increasingly large fibers, one inside another. But determining whether these models are correct has been stymied by the lack of imaging technology that can visualize chromatin.

Electron microscopy, one of the common tools to visualize such minute structures, doesn’t work well with chromatin, O’Shea said. That’s because the chemical elements in chromatin don’t contain many electrons.

The Salk team solved that problem by using a fluorescent dye to stain the chromatin, adding electrons so its pattern can be detected by electron microscopy. They…

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