Figure 1.

Summary of insulator function in nuclear organization and gene expression. A. Linear organization of a typical eukaryotic gene. The RNA coding region of the gene is represented by a green arrow, the transcription complex and RNA polymerase II is denoted by an orange oval and the Mediator complex by a green sphere. The cohesion complex is indicated by a red ring; cohesion is also found at some enhancers (not shown). Enhancers in the upstream regulatory region of the gene are indicated by blue ovals of different hues. Insulators are represented by pink spheres. B. Three-dimensional arrangement of the same region represented in panel A. The 3' region of the gene (terminator) contacts the promoter to form a gene loop, a phenomenon that has been observed more frequently in yeast cells. The most proximal enhancer (E1) contacts Mediator and/or the transcription complex; cohesion stabilizes this interaction. Insulator elements, such as CTCF in vertebrates, contact each other to form a loop; this interaction is also mediated by cohesion. As a consequence of the formation of this loop, Enhancer E2 is unable to act on the promoter of the gene while enhancer E3 is brought close to the promoter to activate transcription. C. Many insulator sites come together at one nuclear location to form insulator bodies. This arrangement is similar to that formed by PREs and PcG proteins, which come together at Pc bodies (see Figure 2C).