A nucleosome is the fundamental repeating unit of DNA organization within the nucleus of eukaryotic cells. Its primary purpose is the initial packaging of vast DNA lengths, ensuring genetic material efficiently fits inside the cell nucleus. Nucleosomes form the basic unit of chromatin, the complex of DNA and proteins that forms chromosomes.
The Building Blocks: DNA and Histones
Nucleosomes are primarily composed of DNA and histone proteins. DNA, the cell’s genetic blueprint, exists as an extremely long, linear molecule. Histones are a specific group of small, positively charged proteins, including H2A, H2B, H3, and H4. Their positive charge allows them to strongly bind to negatively charged DNA, facilitating DNA compaction. The core of a nucleosome forms from two copies of each of these four histone types, creating an octamer.
Assembling the Nucleosome: Structure and Formation
A nucleosome assembles by DNA wrapping around a histone octamer. Approximately 146 to 147 base pairs of DNA coil almost twice in a left-handed superhelical manner around the eight histone proteins. This structure forms a disc-like particle, often visualized as a “bead” on a “string” of DNA. The stretches of DNA connecting these “beads” are known as linker DNA. A fifth histone, H1, known as the linker histone, helps stabilize the nucleosome structure by binding to the linker DNA where it enters and exits the histone core.
The Nucleosome’s Critical Roles
Nucleosomes perform important functions within the cell, particularly in DNA compaction and gene regulation. They are the initial level of DNA packaging, effectively shortening the two meters of DNA in a human cell to fit within a nucleus micrometers in diameter. This compaction reduces the DNA length by approximately seven-fold.
Beyond packaging, the arrangement of DNA around histones significantly influences gene expression. Tightly packed DNA, known as heterochromatin, is less accessible to the cellular machinery responsible for reading genes, leading to gene silencing. Conversely, loosely packed DNA, termed euchromatin, is more accessible and associated with active gene transcription. Chemical modifications to histone tails, such as acetylation or methylation, can alter how tightly DNA is wrapped. For instance, acetylation loosens DNA wrapping, promoting gene activity, while other modifications can lead to tighter packing and gene repression.
From Nucleosomes to Chromosomes
Nucleosomes serve as foundational units for progressively higher levels of DNA organization. The initial “beads-on-a-string” arrangement of nucleosomes can further coil and fold, forming a thicker, more condensed structure known as the 30-nanometer fiber. This 30-nanometer fiber then undergoes additional folding into looped domains. These loops are further organized and compacted, eventually forming the highly condensed, visible structures known as chromosomes, particularly evident during cell division. Nucleosomes are essential for the hierarchy of DNA packaging, enabling the vast genome to fit within the cell nucleus and allowing regulated access to genetic information.