FIGURE 10.05 Methylation of Insulator Sequences and Binding
A) The Igf2 (insulin-like growth factor-II) gene is distant from an enhancer element. B) When the insulator is not methylated, the CTCF protein binds to the insulator and the enhancer can only affect the H19 gene. C) When the insulator and the H19 gene are methylated, the CTCF protein does not bind, allowing the enhancer to activate the Igf2 gene.
Insulators can be inactivated by methylating their CG sequences.
isms, such as the fruit-fly Drosophila, there are not only fixed insulator sequences, but also mobile ones. An example is the co-called gypsy element, which is a retro-transposon and can move from place to place within the genome (see Ch. 15 for transposons).]
In some cases, at least in vertebrates, insulators may be converted between operational or nonoperational forms. Insulators are GC-rich and, as described below, CG sequences may be methylated. When the insulator element is methylated, it no longer binds the CTCF protein and no longer functions (Fig. 10.05). The Igf2 gene (encoding insulin-like growth factor-II) and the H19 gene are close together and face in the same direction. The maternal copy of the Igf2 gene is normally silenced but the paternal copy is active. Conversely, the maternal H19 gene is normally active whereas the paternal copy is silenced. This is due to differing methylation patterns on the maternal and paternal chromosomes (i.e. an imprinting mechanism—see below).
The reason insulators were also called "boundary elements" is because they form boundaries to regions of heterochromatin. In addition to blocking the action of
Although many loops are present, only a single loop of histone-free DNA is drawn coming from a region of the nuclear scaffold. The matrix attachment regions contain matrix attachment proteins (MAR protein) that anchor the DNA to the scaffold.
DNA forms giant loops that are attached to scaffold proteins by special AT-rich sequences.
enhancers, insulators also prevent the spread of heterochromatin and the resultant silencing of genes (see below).
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