The vast amount of genetic material within our cells requires a highly organized system to fit inside the tiny nucleus. This packaging is achieved through structures known as nucleosomes, the fundamental unit for compacting DNA in eukaryotic cells. A nucleosome is analogous to a thread neatly wrapped around a spool.
The Building Blocks of a Nucleosome
The nucleosome is composed of two components: DNA and a specific group of proteins called histones. Histone proteins are small, highly conserved proteins rich in positively charged amino acids like lysine and arginine. This positive charge allows them to strongly associate with the negatively charged phosphate backbone of DNA.
There are five main types of histone proteins involved in nucleosome formation. Four of these, H2A, H2B, H3, and H4, are known as core histones. Two copies of each core histone protein come together to form a protein complex called a histone octamer. This octamer acts as the central scaffold around which the DNA is wrapped.
Assembling the Nucleosome Core Particle
The assembly of a single nucleosome core particle involves DNA winding around this histone octamer. Approximately 147 base pairs of DNA precisely wrap in a left-handed superhelical turn around the outside of the histone octamer. This wrapping creates a disc-shaped structure, measuring about 11 nanometers in diameter and 5.5 nanometers in height.
This compact arrangement represents the first level of DNA compaction within the cell. The precise interaction between the DNA and the histone proteins ensures a stable, uniform structure for each nucleosome core particle. This initial coiling process reduces the overall length of the DNA by several times.
Connecting Nucleosomes to Form Chromatin
Beyond individual nucleosome core particles, DNA packaging continues into a more extended structure known as chromatin. This arrangement is described using the “beads on a string” model, where each nucleosome core particle functions as a “bead.” The DNA segment connecting these beads is referred to as linker DNA, typically ranging from 10 to 80 base pairs in length.
A fifth histone protein, the linker histone H1, aids in further compaction. Histone H1 binds to the linker DNA and to a part of the nucleosome core particle where the DNA enters and exits. This binding helps to pull adjacent nucleosomes closer together, facilitating the formation of a more condensed chromatin fiber, often described as a 30-nanometer fiber.
The Functional Role of Nucleosome Structure
Nucleosome structure serves two functions within the cell. First, nucleosomes are fundamental for DNA compaction, allowing the vast amount of genetic material to fit within the small nucleus. For instance, the approximately two meters of DNA in a human cell must be condensed hundreds of thousands of times to fit into a nucleus that is only about 6-10 micrometers in diameter. This initial level of folding by nucleosomes reduces the DNA length by roughly one-third, providing the basis for higher-order chromatin structures.
Second, nucleosome structure plays a direct role in regulating gene expression. The way DNA is wrapped around the histones dictates its accessibility to the cellular machinery responsible for reading genes, such as RNA polymerase. When DNA is tightly packed around nucleosomes, forming a compact structure called heterochromatin, genes in that region are inaccessible and therefore “off” or inactive. Conversely, when DNA is more loosely associated with nucleosomes, forming a less compact structure known as euchromatin, genes are more accessible and can be “on” or actively transcribed.
Dynamic Modifications to Nucleosome Structure
Nucleosome structure is not static but undergoes constant adjustments to meet the cell’s needs in gene regulation. These dynamic changes are mediated by chemical modifications to the histone proteins. Each core histone possesses flexible “tails” that extend outwards from the nucleosome core.
These histone tails can be modified by various enzymes through processes such as acetylation and methylation. Acetylation, for example, adds an acetyl group to lysine residues on the histone tails, which loosens the interaction between histones and DNA. This loosening makes the DNA more accessible for gene transcription. Methylation, which adds methyl groups, has varied effects, either promoting or hindering gene expression depending on the specific histone and site of modification. These modifications act as signals, influencing whether the chromatin tightens or loosens, thereby precisely controlling which genes are expressed at any given time.