Cell nucleus

The cell nucleus is a defining feature of eukaryotic cell biology and serves as the principal repository for genetic information. It contains the majority of the cell’s DNA, regulates gene expression, and coordinates essential processes such as DNA replication, chromatin organisation, and ribosome assembly. As a membrane-bound organelle, it provides a specialised internal environment distinct from the surrounding cytoplasm, ensuring the integrity and controlled use of genetic material throughout the cell cycle.

Structural Characteristics and General Organisation

The nucleus is typically spherical or ellipsoidal and occupies around one-tenth of the volume of most eukaryotic cells. In human cells, it commonly measures approximately six micrometres in diameter. Although most eukaryotic cells possess a single nucleus, exceptions exist: mammalian red blood cells are anucleated, while certain cell types, such as osteoclasts, are multinucleated. The internal environment of the nucleus, known as the nucleoplasm, contains chromatin, the nucleolus, and numerous non-membranous nuclear bodies.
Two major structures define its architecture: the nuclear envelope and the nuclear matrix. The nuclear envelope is a double membrane system that encloses the genetic material and segregates it from the cytoplasm. The nuclear matrix forms a fibrous framework that provides mechanical support, spatial organisation, and anchoring sites for chromatin and nuclear bodies. Nuclear size correlates with cell size, a relationship known as the nucleus-to-cytoplasm ratio, which varies across species and cell types.

Chromatin, Chromosomes, and Genetic Organisation

Nearly all of the cell’s genome resides within the nucleus, arranged as multiple linear DNA molecules combined with proteins to form chromatin. Each human cell contains approximately two metres of DNA packaged efficiently into chromosomes. During interphase, chromatin exists mainly in two forms:

• Euchromatin, the less compact form, containing genes that are frequently transcribed.
• Heterochromatin, the more densely packed form, largely transcriptionally inactive.

Heterochromatin can be further classified into:

• Constitutive heterochromatin, permanently compacted and associated with structural regions such as telomeres and centromeres.
• Facultative heterochromatin, compacted only in specific cell types or developmental stages.

Chromatin is not randomly dispersed; instead, it arranges itself into discrete regions known as chromosome territories. These territories occupy distinct nuclear zones, with active genes frequently positioned near territory boundaries, facilitating access to transcription machinery. A small proportion of genes are located outside the nucleus, residing within mitochondria.
Chromatin’s fundamental unit is the nucleosome, and antibodies directed against nucleosomal components form the basis of certain autoimmune responses. Antinuclear antibodies, commonly found in disorders such as systemic lupus erythematosus, highlight the clinical significance of nuclear structures in immunopathology.

Nuclear Envelope and Nuclear Pore Complexes

The nuclear envelope comprises an inner and outer membrane separated by the perinuclear space, which is continuous with the lumen of the endoplasmic reticulum. The outer membrane bears ribosomes actively engaged in protein translation, whereas the inner membrane contains specific proteins that anchor chromatin and connect to the nuclear lamina.
Embedded within the envelope are numerous nuclear pore complexes (NPCs), large protein assemblies responsible for selective transport between the nucleoplasm and cytosol. A typical mammalian nucleus contains between 3,000 and 4,000 NPCs, although this number varies widely among cell types. Each NPC is constructed from approximately thirty nucleoporins arranged in an eightfold symmetrical ring shape.
The transport properties of NPCs are crucial for nuclear function. Small ions and molecules diffuse freely, but larger proteins and RNA molecules require active transport mediated by karyopherins, a family of transport receptors. Karyopherins include:

• Importins, which deliver cargo into the nucleus.
• Exportins, which shuttle molecules out.

Some karyopherins recognise their cargo directly, whereas others rely on adaptor proteins. Transport is energy-dependent and essential for gene expression, ribosome biogenesis, and maintenance of chromosomal structure.
Steroid hormones such as cortisol and aldosterone illustrate another transport mechanism: as lipid-soluble molecules, they diffuse freely across membranes and bind nuclear receptors in the cytoplasm. Once bound, these receptors enter the nucleus to regulate transcription; in the absence of ligand binding, many act as histone-deacetylating repressors.

Nuclear Lamina and Mechanical Support

Mechanical integrity of the nucleus is provided by two networks of intermediate filaments: the internal nuclear lamina and a more loosely organised cytosolic support system. The nuclear lamina lies just beneath the inner nuclear membrane and is composed primarily of lamin proteins. Lamins are synthesised in the cytosol and transported into the nucleus, where they assemble into a robust meshwork. They stabilise the nuclear envelope, anchor nuclear pore complexes, and help organise chromatin.
On the outer surface of the envelope, proteins such as emerin and nesprin link the nucleus to the cytoskeleton, enabling mechanotransduction and structural integration with the rest of the cell.

Nuclear Bodies and Subnuclear Structures

Although the nucleus lacks membrane-bound organelles, it contains several distinct nuclear bodies formed by associations of proteins, RNA molecules, and chromosomal fragments. These bodies are functionally specialised and dynamically assembled. Key examples include:

• The nucleolus, the most prominent nuclear body, responsible for rRNA synthesis and ribosomal subunit assembly.
• Cajal bodies, involved in RNA processing and modification.
• Speckles, associated with storage and modification of splicing factors.
• PML bodies, implicated in transcriptional regulation and cellular stress responses.

These structures operate in close coordination with chromatin territories to maintain efficient gene expression and genomic regulation.

Nuclear Transport, Gene Regulation, and Cell Function

The nucleus plays a central role in maintaining genome integrity and regulating the cell’s activities. Controlled movement of molecules ensures that DNA replication, transcription, and RNA processing occur within a highly ordered environment. Regulatory proteins, transcription factors, and RNA species constantly transit through the NPCs to facilitate these processes.
Gene expression is tightly controlled by interactions between chromatin structure, nuclear body organisation, and signalling pathways. External signals, including steroid hormones and growth factors, influence nuclear function through receptor-mediated transcriptional activation or repression. The structural arrangement of euchromatin and heterochromatin, along with the dynamic positioning of chromosomes, is essential for efficient gene regulation.

The Nucleus in the Context of the Cell Cycle

Cytological staining techniques such as Hoechst staining allow clear visualisation of DNA within the nucleus. In interphase cells, the dye uniformly labels the extended chromatin, whereas in mitotic cells the condensed chromosomes appear as discrete, brightly stained structures. This transformation illustrates the dramatic reorganisation that the nucleus undergoes during the cell cycle to ensure accurate chromosome segregation.