histone
Meaning of histone: Packing is only half the point, since how tightly DNA is wound decides which genes can be reached and read.
Definition of histone
A histone is one of a family of small proteins that DNA winds around inside the cell nucleus. Eight of them form a spool and the DNA makes roughly two turns about it, a repeating unit called a nucleosome. Coiling this way packs an enormous length of DNA into a tiny space and governs which stretches can be read.
How does so much DNA fit inside a cell?
The DNA in a single human cell would stretch to about two meters if pulled straight, and it has to fit inside a nucleus too small to see without a microscope. Histones make that possible. Four kinds pair up to form the spool, a fifth clamps the DNA where it enters and leaves, and the resulting beads coil into thicker fibers that fold again into the chromosomes visible when a cell divides. DNA carries a negative charge and histones a positive one, so the two grip each other by simple electrical attraction. That grip is also the point at which the arrangement can be adjusted.
How do histones control gene activity?
| Chemical mark | Effect on packing | Usual consequence |
|---|---|---|
| Acetyl group added | Neutralizes charge and loosens the grip | The region opens and genes there can be read |
| Acetyl group removed | Restores the grip and tightens the coil | The region closes and genes fall silent |
| Methyl group added | Varies with the exact position marked | Can either activate or silence |
The tails of the histone proteins stick out from the spool and carry these marks. The enzyme histone deacetylase strips acetyl groups away and so closes regions down, while a counterpart adds them. Because the marks change gene activity without altering the DNA sequence itself, and because they are copied when a cell divides, they are the central example of what is meant by an epigenetic change.
Why are they a drug target?
Cancer cells frequently silence genes that would otherwise restrain their growth, and they do it by tightening the packing rather than by deleting anything. A histone deacetylase inhibitor blocks the enzyme that maintains that tightening, allowing the region to open again. Drugs of this class are in clinical use for certain lymphomas and for myeloma. The appeal of the approach is that nothing in the sequence has to be repaired; what was switched off can in principle be switched back on.
Used in a sentence
The research described changes in histone modification patterns within the tumor sample.
Good to know
Histones influence gene activity indirectly, by controlling how tightly DNA is packaged, which distinguishes their role from that of transcription factors, proteins that bind DNA directly to switch particular genes on or off.