Organizing and condensing chromosomes

Loops do more than save space. How chromatin is folded decides which stretches of DNA can reach each other and which genes can be used. Then, when a cell divides, the whole arrangement is torn down and rebuilt into compact, X-shaped chromosomes.

Topologically associating domains

Researchers can map which pieces of DNA physically touch inside the nucleus. These maps show chromatin divided into loop domains called topologically associating domains (TADs). Pieces of DNA inside one TAD contact each other far more often than they contact DNA in the neighboring TADs.

A typical TAD spans 100,000 to 1 million base pairs (100 kb to 1 Mb, where 1 kb is 1,000 base pairs and 1 Mb is 1,000,000) and holds 1 to 5 genes. Its boundaries are set by SMC proteins and CTCFs, the same loop-building team from the last segment. Inside a TAD, smaller loops form when proteins bound to different DNA sites grip each other, such as proteins that help turn genes on.

TAD boundaries have two effects:

• They bring things together. Grouping a gene with the DNA sequences that control it helps the gene be regulated properly.
• They keep things apart. A control sequence in one TAD can’t affect a gene in another TAD. A structure that limits genetic interactions to one region like this is called an insulator.

Euchromatin and heterochromatin

Most of a cell’s life is spent in interphase, the period when it isn’t dividing and its chromosomes sit inside the nucleus. Even then, packing varies along each chromosome, and the difference is visible under a light microscope.

Four levels of organization in the nucleus

During interphase, chromosome organization can be described at four nested levels, from largest to smallest:

Metaphase chromosomes: maximum packing

When a cell gets ready to divide, its chromosomes compact much further. By metaphase, the stage of division when chromosomes line up in the middle of the cell, each one is a short, X-shaped structure. The X is two identical copies, called chromatids, made during replication and joined at a constricted point called the centromere. Each chromatid is about 700 nm wide, so the pair is about 1,400 nm across. A metaphase chromosome is far smaller than the territory the same chromosome fills during interphase.

Two protein complexes, condensin I and condensin II, drive this compaction. Both contain SMC proteins, the same kind of ring-forming protein that builds loops during interphase.

The finished arrangement, loops radiating outward from a central helical scaffold, is a radial loop array. Picture a spiral staircase with large loops of rope hung from its railing, each big loop gathered into smaller loops of its own.

Check yourselfWhat are the two jobs of condensin II in forming a metaphase chromosome, and how does condensin I add to them?

Condensin II forms the helical protein scaffold and creates large loops (about 400 kb) anchored to it. Condensin I then makes smaller loops (about 80 kb) within those large loops, compacting the chromosome further.