Enhancers and Insulator Sequences Segregate DNA Functionally

Enhancers may be found up to several kilobases distant and either upstream or downstream from the promoters they control. This is done by looping of DNA around so that the activator proteins bound at the enhancer can make contact with the transcription apparatus via the mediator complex as discussed above (Fig. 10.03).

This looping mechanism allows a single enhancer to control several genes in its vicinity. But how is an enhancer prevented from activating genes further along the chromosome, that are supposed to be under control of another, closer enhancer? It appears that chromosomes are divided into regulatory neighborhoods by special sequences known as "boundary elements," or insulators (Fig. 10.04). An enhancer is prevented from controlling a gene if an insulator sequence lies between them on the chromosome.

insulator A DNA sequence that shields promoters from the action of enhancers and also prevents the spread of heterochromatin

FIGURE 10.03 Activator Proteins and the Mediator

A) The folding of the DNA allows numerous activators that are bound to enhancer sequences to approach the transcription apparatus. B) The mediator complex allows contact of the activators and/or repressors with the DNA polymerase.

FIGURE 10.04 Insulator Sequences Restrict the Range of Enhancer Action

A large loop of DNA is shown with an enhancer that may interact with Gene X or Gene Y. Insulator sequences at the base of the loop are recognized by an IBP (insulator binding protein) which prevents the enhancer from acting outside of the loop.

FIGURE 10.04 Insulator Sequences Restrict the Range of Enhancer Action

A large loop of DNA is shown with an enhancer that may interact with Gene X or Gene Y. Insulator sequences at the base of the loop are recognized by an IBP (insulator binding protein) which prevents the enhancer from acting outside of the loop.

Insulators are regions of DNA consisting of clusters of sequences that bind multiple copies of special zinc-finger proteins known as insulator binding proteins (IBPs). In vertebrates, the best known of these is CTCF (CCCTC-binding Factor). These must bind to the insulator sequences to block enhancer action. [In some organ-

insulator binding protein (IBP) Protein that binds to insulator sequence and is necessary for the insulator to function

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