Setting up and maintaining differential insulators and boundaries for genomic imprinting

Abstract

It is becoming increasingly clear that gene expression is strongly regulated by the surrounding chromatin and nuclear environment. Gene regulatory elements can influence expression over long distances and the genome needs mechanisms whereby transcription can be contained. Our current understanding of the mechanisms whereby insulator/boundary elements organise the genome into active and silent domains is based on chromatin looping models that separate genes and regulatory elements. Imprinted genes have parent-of-origin specific chromatin conformation that seems to be maintained in somatic tissues and reprogrammed in the germline. This review focuses on the proteins found to be present at insulator/boundary sequences at imprinted genes and examines the experimental evidence at the IGF2-H19 locus for a model in which CTCF or other proteins determine primary looping scaffolds that are maintained in most cell lineages and speculates how these loops may enable dynamic secondary associations that can activate or silence genes.