Friday, December 11, 2009

Chromatin Compartments

The fractal packing of some DNA is just one of the interesting results from the recent Science paper by Lieberman-Aiden and colleagues. Of greater practical importance is the ability of their experimental technique to assign each region of DNA to one of two compartments.

The fact that some DNA regions, called heterochromatin, are packed more densely than other regions, called euchromatin, was discovered 80 years ago, by observing darker and lighter regions of stained nuclei under the optical microscope. Researchers have since learned that the heterochromatin is more densely packed, and that the genes it contains are transcriptionally silent. Heterochromatin also tends to segregate to the periphery of the nucleus, but to avoid the nuclear pores through which gene products are exported.

The Science authors did not mention this well-known classification. However, when they measured which regions of the genome were close together in the clumped DNA, they found that they could divide the mappable regions of the genome into two distinct "compartments." Regions from compartment A were more likely to lie close to other regions from compartment A, and similarly for compartment B. Importantly, they could make this assignment even for regions on different chromosomes, suggesting that the compartments represent regions of the nucleus in which segments of different chromosomes mingle.

The researchers also found that regions in compartment B were much more likely to be in close contact, so they designated that compartment "closed," and the other one "open." But Erez Lieberman-Aiden told me that "it seemed best to use terminology attached to things that we can probe and which clearly correspond to our compartments." Indeed, the regions they call "open" correspond well to the regions that can are accessible to DNA-digesting enzymes, but do not correspond to the light and dark bands that appear on the chromosomes during cell division.

Although the relationship to microscopically-observed partitioning may need clarification, the ability to globally map closed and open regions of the genome could be a very powerful tool. Looking at different cell types, for example, could reveal overall "signatures" in the chromosome arrangements. Such cell-type-specific patterns are already known to exist in the arrangement of histone modifications, which affect the nucleosome arrangement.

In addition, the chromatin structure enters into regulation of individual genes. Enhancer elements in the DNA sequence, for example, can affect the expression of quite distant genes, while an intervening insulator region can block that effect. Models of these influences generally involve large loops of DNA, but some also include the notion of a densely-packed and transcriptionally silent "scaffold" region that is reminiscent of the closed compartment. Determining which sections of the sequence are in the closed or open arrangements, especially in cells with different types of activity, could add some much-needed experimental visibility into the regulatory activity of these critically important elements.

[For physicist readers: as I was wrapping up this entry, the latest Physics Today arrived with a news story on this subject.]

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