A description of the packaging mechanisms that allow all 3 billion bases of the human genome to fit into the small mammalian nucleus.
How does the DNA fit inside the nucleus?
Although the nucleus occupies around 10% of the volume of a mammalian cell, it is still only approximately 6µm, or 6 thousandths of a millimetre, in diameter. The human genome, however, is over two metres in length. For a long time, its ability to fit inside the cell seemed miraculous.
The DNA manages to fit inside the nucleus by virtue of being very efficiently packaged. DNA in the nucleus is associated with histone proteins. Histones usually form dimers, which then come together to form an octomeric particle made of four histone pairs. DNA associates with and can wrap around this particle 1.65 times, which corresponds to 147 bases of DNA. This is known as a nucleosome, and is the first stage in condensing the DNA down to a manageable size. Under transmission electron microscopy, the nucleosomes appear as ‘beads on a string’. These ‘beads on a string’ then coil upon themselves, forming a higher-order structure known as the 30 nanometre fibre, or chromatin. The exact organisation of this fibre is not yet known, although the specialised linker histone, H1, is thought to play a key role. The 30nm fibre is sometimes referred to as the ‘solenoid’, due to its presumed coiling structure. It can unwind and loosen to allow access for enzymes involved in transcription.
The 30nm fibre is condensed further by scaffold proteins, forming a string which the 30nm fibre loops in and out of, further reducing its size. The loops average 300nm in length. It is the combination of all of these different coiling and condensing techniques that allow the entire human genome to fit inside the nucleus. During metaphase, the stage of the cell cycle preceding cell division, the chromatin condenses even further, coiling the 300nm fibre about itself and taking on its most condensed form. At this point it is so dense that the individual chromosomes separate and become visible under a light microscope.