The role of insulator elements in large-scale chromatin structure in interphase

Abstract

Insulator elements can be classified as enhancer-blocking or barrier insulators depending on whether they interfere with enhancer-promoter interactions or act as barriers against the spreading of heterochromatin. The former class may exert its function at least in part by attaching the chromatin fiber to a nuclear substrate such as the nuclear matrix, resulting in the formation of chromatin loops. The latter class functions by recruiting histone-modifying enzymes, although some barrier insulators have also been shown to create chromatin loops. These loops may correspond to functional nuclear domains containing clusters of co-expressed genes. Thus, insulators may determine specific patterns of nuclear organization that are important in establishing specific programs of gene expression during cell differentiation and development.

Figure 1. Insulator elements organize the chromatin fiber in the nucleus by establishing separate compartments of higher-order chromatin structure

(A) Domains of open chromatin (yellow nucleosomes) are flanked by insulators (pink, blue and green spheres) that interact together to form a loop. (B) Diagram showing part of a nucleus with compartmentalized chromatin, anchored in part to the nuclear periphery by interactions of the insulators with the nuclear lamina (red lines).

Figure 2. Insulator activity can be regulated by ubiquitination and sumoylation of insulator proteins

A. Two active insulators coming together at an insulator body. dTopors is present at the insulator sites, Rm62/Lip is not present, Su(Hw) is ubiquitinated, Mod(mdg4)2.2 and CP190 are not sumoylated and dTopors serves as a bridge to the lamina. B. Two inactive insulators that cannot be part of an insulator body. dTopors is absent and Su(Hw) is not ubiquitinated, whereas Mod(mdg4)2.2 and CP190 are sumoylated. Rm62/Lip is present and bound to RNA. Under these conditions, the two insulator sites cannot interact and form insulator bodies. Absence of dTopors also precludes interactions with the lamina.