Genomic Imprinting

Abstract

Gene regulation occurs in the context of the epigenome, i.e., in regions of accessible euchromatin that are surrounded by inaccessible heterochromatin. Insulators are genomic loci that separate genes located in one chromatin region from promiscuous regulation by transcription factors binding to enhancers of neighboring chromatin regions. The genome regulator CTCF has tens of thousands DNA binding sites in human cells, many of which are located in inter-genic regions, such as insulators. Most of these sites are at the border of distinct chromosomal domains.

The main function of CTCF is to mediate intra- and inter-chromosomal contacts and in this way to stabilize 3-dimensional complexes of chromatin loops (for more details see Chap. 12). CTCF-mediated loops at several developmentally regulated loci provide a mechanistic explanation of genomic imprinting. Moreover, CTCF-stabilized higher-order chromatin structures are heritable carriers of epigenetic information. This suggests that CTCF has a key role in the organization of chromatin architecture.

In this chapter, we present CTCF as the critical nuclear protein for mediating the function of insulators. We will discuss different types of insulators and the role of chromatin loops in genomic imprinting. In this context, we will demonstrate that CTCF binding represents a heritable epigenetic component in the complex interplay between higher-order chromatin structure, DNA methylation and developmentally regulated gene expression.