5.9: Chromatin Packaging

Each human somatic cell contains 6 billion base-pairs of DNA. Each base-pair is 0.34 nm long, which means that each diploid cell contains a staggering 2 meters of DNA. How is such a long DNA strand packed inside a nucleus measuring only 10 - 20 microns in diameter?

The chromatin

In combination with specialized DNA binding protein called Histones, the DNA double helix forms a compact DNA: protein complex called chromatin. The chromatin itself is further compacted into higher-order structures. The highest level of compaction is achieved during the cell cycle's metaphase, where the chromatin condenses to form the chromatids of a chromosome.

Nucleosomes

Nucleosomes are the basic functional and repeating unit of chromatin. A nucleosome consists of 8 histone proteins wound around by 147 base pairs of DNA. Under electron microscopy, the chromatin appears as a structure resembling beads on a string due to nucleosomes' presence along its length. This packaging shortens the fiber length by seven-fold.

Solenoid model

The nucleosomes are further coiled into 30 nm fibers, so-called because of their diameter of approximately 30 nm. Such a compaction is explained by a widely accepted hypothesis - the solenoid model. A solenoid refers to the structure of a wire coiled on a central axis. This model proposes that nucleosomes are arranged in a left-handed helical conformation with six or more nucleosomes per turn. One of the non-core histone proteins, H1, plays an essential role in nucleosome compaction; in its absence the chromatin fiber turns into irregular clumps of nucleosomes.

Chromatin packaging is an active area of research. The new emerging data has allowed scientists to view chromatin and nucleosomes not as highly defined structures, but rather as a continuum of various inter-convertible conformations at all chromatin packaging stages.

Every human diploid cell contains about 2 meters of DNA compressed inside a tiny nucleus of just a few microns in diameter. The arrangement and coiling of DNA inside the nucleus is therefore highly organized, and tightly regulated.

First, the chromosomal DNA is associated with histone proteins to form a structure called the chromatin. The basic structural and functional unit of chromatin is called a nucleosome. The association of the DNA into nucleosomes shortens the DNA length sevenfold. 

Next, a non-core histone protein called H1 binds to each nucleosome. The H1 histone changes the DNA path as it exits the nucleosome, helping to further compact the complex.

These nucleosomes are then stacked on top of each other, generating a shorter and thicker fiber with a diameter of 30 nm, known as 30-nm fibers.  

The arrangement of nucleosomes into the 30-nm fiber is explained by a widely accepted Solenoid model. The model proposes that nucleosomes are arranged in a left-handed helical conformation with six or more nucleosomes per turn. This shortens the DNA length by a further 50-fold.

Any chromatin region that is not being actively transcribed or replicated exists in the 30-nm fiber form. On the other hand, the chromatin regions that are actively being accessed exist in an extended beads-on-a-string form. 

The 30 nm fibers are coiled further to form loops of around 300 nm length. These fibers are then compressed into 250 nm wide coils.

Later during the metaphase of the cell cycle, the chromatin fibers form highly condensed structures called chromosomes. 

The overall compaction ratio of DNA into the chromosome is approximately 1:10000. Once the cell divides, the chromosomes uncoil again.