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Biology · Ch 5 — Molecular Basis of Inheritance

Packaging of DNA — Nucleosomes and Chromatin

5.7

Packaging of DNA — Nucleosomes and Chromatin

A single human cell contains roughly two metres of DNA in total, yet this enormous length must somehow be folded and compacted to fit inside a nucleus only a few micrometres across — a packaging problem of extraordinary scale. Simply coiling the DNA on itself would not be nearly enough; the cell instead relies on a hierarchy of DNA-protein packaging, in which specialised proteins organise the DNA into progressively more compact structures.

The first and most fundamental level of this packaging involves a family of small, positively charged proteins called histones. Histones are rich in the basic (positively charged) amino acids lysine and arginine, which gives the histone protein an overall positive charge; DNA, by contrast, carries a strong overall negative charge along its sugar-phosphate backbone (because of the many phosphate groups), so histones and DNA are held together by a strong electrostatic (ionic) attraction between the oppositely charged molecules. Four different histone proteins — H2A, H2B, H3 and H4 — associate together, two copies of each, to form a disc-shaped complex of eight histone protein molecules called a histone octamer.

Roughly 146 to 147 base pairs of DNA wind around the outside of one such histone octamer, making almost two complete turns, to form the basic repeating packaging unit of chromatin, called a nucleosome. Nucleosomes occur repeatedly along the length of a DNA molecule, connected to one another by short stretches of "linker" DNA that are not wound around a histone octamer; under an electron microscope, this repeating structure gives chromatin the appearance of "beads on a string," with each nucleosome forming one bead and the linker DNA between successive nucleosomes forming the connecting string. A fifth type of histone protein, H1, sits on the outside of the nucleosome, at the point where the DNA enters and leaves the histone octamer, and helps to further condense the string of nucleosomes into a more tightly coiled, higher-order structure. …

Figure 5.4The Nucleosome — Beads-on-a-String Packaging of DNA

What this figure shows. A diagram showing a stretch of DNA double helix wound almost twice around a disc-shaped histone octamer (drawn as eight small circles stacked in two layers of four, representing two copies each of histones H2A, H2B, H3 and H4) to form one nucleosome bead; several such nucleosome beads are shown strung along the DNA at regular intervals, connected by short stretches of unwound linker DNA, giving the classic 'beads on a string' appearance, with a single H1 histone drawn as a small circle sitting at the point where the DNA enter …