Genome Organization & Chromatin

the nucleosome

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Think of a long thread that needs to be stored without tangling, so you wind short lengths of it around a row of small spools. That is essentially the cell's first move in packaging DNA. The basic repeating unit of this winding is the nucleosome, and under the electron microscope a stretch of it really does look like beads on a string.

Each nucleosome is a spool made of eight histone proteins (a histone octamer: two copies each of H2A, H2B, H3, and H4) with about 147 base pairs of DNA wrapped almost twice around the outside, like thread around a bobbin. Between one nucleosome and the next runs a short piece of 'linker' DNA, and a fifth histone, H1, clamps the DNA where it enters and exits, helping the beads draw closer together. DNA is negatively charged and histones are rich in positively charged amino acids, so the two attract — this electrostatic grip is what lets the spool hold the thread. Nucleosomes achieve the first level of compaction, shrinking the DNA's length roughly sixfold.

Nucleosomes are far more than passive packing. Their position along the DNA, and how tightly they grip, decide whether the machinery that reads genes can reach the sequence underneath. Cells actively slide, evict, and chemically tag nucleosomes to open or close regions of the genome, which makes the nucleosome the front line of how chromatin controls gene access. A promoter buried under a tightly positioned nucleosome is hard to switch on; one in a nucleosome-free gap is exposed and ready.

Picture 147 base pairs of DNA wrapped 1.7 turns around a disc of eight histones, then a short bare linker, then the next bead — repeated millions of times. Digesting the linker DNA with an enzyme leaves the protected 147-base-pair beads, which is how the nucleosome was first measured.

The nucleosome — DNA wound around a histone octamer — is the basic unit of chromatin.

A nucleosome is not a permanent knot. Cells slide, remove, and re-deposit nucleosomes constantly, and this dynamic positioning is itself a way of controlling which genes are accessible.

Also called
beads on a stringhistone octamer with DNA核小体核小體