How to stuff two meters of DNA into a nucleus
A. Sanborn and E.L. Aiden
If packing a vacation’s worth of clothes into a small carry-on bag seems daunting, consider a cell’s task. Nearly every cell in the body carries 6 billion DNA base pairs. When stretched out, the DNA would extend about two meters. Cells must compress all that genetic material into a nucleus that measures only about 5 micrometers across. That’s like packing a thread the length of two football fields into a sphere no wider than the point of a pin.
To accomplish the feat, cells make loops in the DNA. Scientists used to think there must be hundreds of thousands or even millions of loops, but a new study shows that there are only about 10,000 nonoverlapping loops in each cell. Each loop (gray, top left) is anchored by small stretches of DNA (black) where proteins called transcription factors bind (blue, middle left). The loop crumples into a blob and gets coated with one of several chemical tags (red, orange and green, bottom left) that tell the cell whether to turn genes on or off.
Coated loops group together in subcompartments with other loops bearing the same coating, a team including structural biologist Suhas Rao of Baylor College of Medicine in Houston and computational biologist Miriam Huntley of Harvard University report in the Dec. 18 Cell.
A computer simulation shows one way a stretch of 5 million DNA bases may fold inside the nucleus. Each type of cell may pack the DNA slightly differently, much the way an origami artist can fold a piece of paper into many shapes.