Within each cell lies an astonishingly long molecule: deoxyribonucleic acid, or DNA. If the DNA from just one human cell were uncoiled, it would measure approximately 2 meters (about 6.5 feet) in length. This immense length presents a significant challenge for the microscopic confines of a cell’s nucleus, typically only 5 to 10 micrometers across. To fit this genetic material efficiently into such a tiny space, a highly organized system of packaging is necessary.
What Histone Subunits Are
The precise organization of DNA within the cell nucleus relies on a family of specialized proteins called histones. These small, positively charged proteins are found within the chromosomes of eukaryotic cells. Their positive charge comes from being rich in basic amino acids like lysine and arginine. This charge is crucial because DNA carries a negative charge due to its phosphate backbone, allowing for a strong electrostatic attraction.
There are five main types of histone proteins: H1, H2A, H2B, H3, and H4. H2A, H2B, H3, and H4 are known as “core histones” because they form the central structural unit around which DNA is wrapped. The H1 histone, a “linker histone,” plays a distinct role in stabilizing the larger DNA-protein complex. Histones are fundamental components of chromatin, the complex of DNA and proteins that makes up chromosomes.
Assembling the Nucleosome
Core histone subunits form the fundamental repeating unit of chromatin, known as the nucleosome. Two copies of each core histone (H2A, H2B, H3, and H4) combine to form an octamer, a complex of eight histone proteins. This histone octamer acts as a spool.
Approximately 146 to 147 base pairs of DNA wrap almost two full turns (1.65 to 1.67 left-handed superhelical turns) around this histone octamer. This wrapping forms the nucleosome core particle. The structure resembles “beads on a string,” with nucleosomes as the beads and connecting DNA as linker DNA. The H1 linker histone binds where DNA enters and exits the nucleosome, securing it and stabilizing this initial compaction.
Compacting Our Genetic Material
Nucleosome formation is the first step in compacting the long DNA molecule. This initial coiling significantly reduces the DNA’s length, allowing it to begin fitting within the cell nucleus. Imagine storing a long thread in a small room; winding it onto tiny spools would be the first logical step, much like DNA wrapping around histone octamers.
Beyond this “beads-on-a-string” arrangement, nucleosomes organize into progressively more compact structures. They coil into a thicker fiber, typically around 30 nanometers in diameter, known as the 30-nanometer chromatin fiber. This fiber then forms larger loops and domains, eventually condensing into the highly compact structures visible during cell division: chromosomes. This hierarchical packaging allows the 2 meters of DNA in each cell to be reduced to 9 micrometers of chromatin fiber when fully condensed. This packaging is dynamic, allowing regions of DNA to become accessible when needed for cellular processes.
Controlling Gene Expression
Beyond their physical role in packaging, histone subunits and nucleosomes play an important role in controlling gene expression. The degree to which DNA is packed around histones directly influences whether genes are active or inactive. Tightly packed DNA, known as heterochromatin, makes genes largely inaccessible to cellular machinery, effectively silencing their expression. Heterochromatin typically appears as darkly stained, dense regions under a microscope.
Conversely, loosely packed DNA, called euchromatin, allows easy access for enzymes and proteins to interact with the DNA, enabling active gene expression. Euchromatin often appears as lightly stained regions. Chemical modifications to histone subunits, particularly on their “tails,” act as molecular switches that regulate this accessibility. For example, acetylation, the addition of an acetyl group to lysine residues on histone tails, neutralizes the histone’s charge, weakening its grip on DNA and promoting a more open, accessible chromatin structure, thereby increasing gene expression. In contrast, methylation, the addition of methyl groups, can either promote or repress gene expression depending on the specific histone and amino acid residue modified. These modifications allow precise regulation of gene activity, which is important for processes like cell differentiation, development, and overall cellular health.