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The Nucleus

The nucleus is the hallmark of eukaryotic cells; the very term eukaryotic means having a "true nucleus".

The Nuclear Envelope

The nucleus is enveloped in a pair of membranes enclosing a lumen that is continuous with that of the endoplasmic reticulum. However, the nuclear envelope is perforated by thousands of nuclear pore complexes (NPCs) that control the passage of molecules in and out of the nucleus.


The nucleus contains the chromosomes of the cell. Each chromosome consists of a single molecule of DNA complexed with an equal mass of proteins. Collectively, the DNA of the nucleus with its associated proteins is called chromatin.

Most of the protein consists of multiple copies of 5 kinds of histones. These are basic proteins, bristling with positively charged arginine and lysine residues. (Both Arg and Lys have a free amino group on their R group, which attracts protons (H+) giving them a positive charge.) Just the choice of amino acids you would make to bind tightly to the negatively-charged phosphate groups of DNA.

Chromatin also contains small amounts of a wide variety of nonhistone proteins. Most of these are transcription factors (e.g., the steroid receptors) and their association with the DNA is more transient.


Two copies of each of four kinds of histones form a core of protein, the nucleosome core. Around this is wrapped 146 base pairs of DNA.

From 50-200 bp of DNA link one nucleosome to the next. Each linker region is occupied by a single molecule of histone 1 (H1).

The binding of histones to DNA does not depend on particular nucleotide sequences in the DNA but does depend critically on the amino acid sequence of the histone. Histones are some of the most conserved molecules during the course of evolution. Histone H4 in the calf differs from H4 in the pea plant at only 2 amino acids residues in the chain of 102.

This electron micrograph (courtesy of David E. Olins and Ada L. Olins) shows chromatin from the nucleus of a chicken red blood cell (birds, unlike most mammals, retain the nucleus in their mature red blood cells). The arrows point to the nucleosomes. You can see why the arrangement of nucleosomes has been likened to "beads on a string".

The formation of nucleosomes helps somewhat, but not nearly enough, to make the DNA sufficiently compact to fit in the nucleus. In order to fit 46 DNA molecules (in humans) averaging 5 cm in length into a nucleus that may be only 10 µm across requires more extensive folding and compaction. Lengths of nucleosomes are coiled together producing a compact fiber 30 nm in diameter. These fibers appear to be folded into a series of tight loops extending from a central protein scaffold.

Histone Modifications

Although their amino acid sequence (primary structure) is unvarying, individual histone molecules do vary in structure as a result of chemical modifications that occur later to individual amino acids.

These include adding: Although 75-80% of the histone molecule is incorporated in the core, the remainder - at the N-terminal - dangles out from the core as a "tail" (not shown in the figure).

The chemical modifications occur on these tails, especially of H3 and H4. The changes are reversible. For example, acetyl groups are

More often than not, these modifications occur on histones in regions of chromatin that become active in gene transcription. This makes a kind of intuitive sense as But there is surely more to the story. In any case, it is now clear that histones are a dynamic component of chromatin and not simply inert DNA-packing material.

So stay tuned.

The Nucleolus

During the period between cell divisions, when the chromosomes are in their extended state, 1 or more of them (10 in human cells) have loops extending into a spherical mass called the nucleolus. Here are synthesized three (of the four) kinds of RNA molecules (28S, 18S, 5.8S) used in the assembly of the large and small subunits of ribosomes. (The 5S rRNA molecules are synthesized at other locations in the nucleus.)

28S, 18S, and 5.8S ribosomal RNA is transcribed (by RNA polymerase I) from hundreds to thousands of tandemly-arranged rDNA genes distributed (in humans) on 10 different chromosomes. The rDNA-containing regions of these 10 chromosomes cluster together in the nucleolus.

Once formed, the rRNA molecules associate with the dozens of different ribosomal proteins used in the assembly of the large and small subunits of the ribosome.

But all proteins are synthesized in the cytosol - and all the ribosomes are needed in the cytosol to do their work - so there must be a mechanism for the transport of these large structures in and out of the nucleus. This is one of the functions of the nuclear pore complexes.

Nuclear Pore Complexes (NPCs)

The nuclear envelope is perforated with thousands of pores.

Each is constructed from a number (30 in yeast; probably around 50 in vertebrates) different proteins called nucleoporins.

The entire assembly forms an aqueous channel connecting the cytosol with the interior of the nucleus ("nucleoplasm"). When materials are to be transported through the pore, it opens up to form a channel some 25 nm wide - large enough to get such large assemblies as ribosomal subunits through.

Transport through the nuclear pore complexes is active; that is, it requires

Import into the nucleus

All proteins are synthesized in the cytosol and those needed by the nucleus must be imported into it through the NPCs. Probably each of these proteins has a characteristic sequence of amino acids that targets it for entry.

They include:

Export from the nucleus

Molecules and macromolecular assemblies exported from the nucleus include:

Both the RNA and protein molecules contain characteristic nuclear export signals needed to ensure their association with the right carrier molecules to take them out to the cytosol.


The term "nucleoplasm" is still used to describe the contents of the nucleus. However, the term disguises the structural complexity and order that seems to exist within the nucleus. For example, there is evidence that DNA replication and transcription occur at discrete sites within the nucleus.
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1 November 2000