enhancer

Suppose the switch for a lamp in your living room could be mounted in the kitchen, or upstairs, or even facing backwards on the wall, and still work the lamp. That would seem absurd for wiring, but it is exactly how many genes are controlled. An enhancer is a short stretch of DNA that boosts a gene's transcription even though it can sit far away from the gene, before it or after it, and in either orientation.

An enhancer is a cluster of binding sites for transcription factors — a patch of DNA, often a few hundred letters long, holding a handful of recognition sequences. When the right activators are present in the cell, they bind these sites and assemble into a little knot of protein. The puzzle of how a switch thousands or even a million letters away reaches its gene is solved by DNA looping: the chromosome bends back on itself so that the enhancer, with its bound activators, is brought into physical contact with the gene's promoter, while the intervening DNA bulges out as a loop. The Mediator complex and architectural proteins help hold the loop, and the activators then deliver their boost to the polymerase at the promoter. Whether a loop forms is itself controlled, and the reach of an enhancer is usually fenced in by insulators so it acts only on the right genes.

Enhancers are where most of the action of animal gene regulation actually lives. A single gene may answer to many enhancers, each a separate module turning the gene on in a different tissue or moment — one enhancer for the developing heart, another for the limb, another for stress. This modularity is why mutations in enhancers, not in the protein-coding gene itself, underlie a great many differences between individuals and species, and many diseases: the protein is fine, but it is made in the wrong place, at the wrong time, or the wrong amount. Much of what makes a human different from a chimpanzee is thought to be enhancer changes, not protein changes.