Insulators: many functions, many mechanisms

  1. Adam G. West1,
  2. Miklos Gaszner1, and
  3. Gary Felsenfeld2
  1. Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-0540, USA

This extract was created in the absence of an abstract.

Eukaryotic genomes are organized into domains containing individual genes and gene clusters that have distinct patterns of expression both during development and in differentiated cells. These genomes contain regulatory elements such as enhancers that are able to activate target genes in cis over considerable distances. They may also contain extended regions of condensed chromatin capable of encroaching on adjacent domains to perturb gene expression. There are a number of ways in which individual domains could be maintained independent of their surroundings through the establishment of boundaries. These boundaries might be variable in position, and established through a balance between countervailing processes (such as condensation and decondensation of chromatin domains). Alternatively, specific DNA sequences and associated proteins might have the role of establishing fixed boundaries.

“Insulator” is the name given to a class of DNA sequence elements that possess a common ability to protect genes from inappropriate signals emanating from their surrounding environment. A useful distinction may be made between the two ways in which insulators protect an expressing gene from its surroundings. The first way is by blocking the action of a distal enhancer on a promoter (Geyer and Corces 1992; Kellum and Schedl 1992). Enhancer blocking only occurs if the insulator is situated between the enhancer and the promoter, not if it is placed elsewhere. Such activity can prevent an enhancer from activating expression of an adjacent gene from which it is blocked, while leaving it free to stimulate expression of genes located on its unblocked side (Fig. 1A). The second way in which insulators protect genes is by acting as “barriers” (Sun and Elgin 1999) that prevent the advance of nearby condensed chromatin that might otherwise silence expression. Some insulators are able to act both as enhancer blockers and barriers (Table1).Others, particularly in yeast, serve …

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