How imprinting centres work

Abstract

Imprinted genes tend to be clustered in the genome. Most of these clusters have been found to be under the control of discrete DNA elements called imprinting centres (ICs) which are normally differentially methylated in the germline. ICs can regulate imprinted expression and epigenetic marks at many genes in the region, even those which lie several megabases away. Some of the molecular and cellular mechanisms by which ICs control other genes and regulatory regions in the cluster are becoming clear. One involves the insulation of genes on one side of the IC from enhancers on the other, mediated by the insulator protein CTCF and higher-order chromatin interactions. Another mechanism may involve non-coding RNAs that originate from the IC, targeting histone modifications to the surrounding genes. Given that several imprinting clusters contain CTCF dependent insulators and/or non-coding RNAs, it is likely that one or both of these two mechanisms regulate imprinting at many loci. Both mechanisms involve a variety of epigenetic marks including DNA methylation and histone modifications but the hierarchy of and interactions between these modifications are not yet understood. The challenge now is to establish a chain of developmental events beginning with differential methylation of an IC in the germline and ending with imprinting of many genes, often in a lineage dependent manner.

Effect of high fat diet on paternal sperm histone distribution and male offspring liver gene expression

“…37 The differential gene expression is regulated by a short DNA sequence, the imprinting center region, which shows differential methylation. 38 Deletion of the imprinting center causes disruption of the parent-specific gene expression pattern. These critical sequences acquire de novo CG methylation in the parental germ line, according to the sex of the parent.…”

“…Using bisulfite sequencing, we examined CG methylation at 7 known Imprinting Control Regions (ICRs) that show complete CG methylation in sperm or are excluded from CG methylation in sperm. 38 The ICR upstream of the H19 gene (which encodes a long non-coding RNA) controls the expression of H19 and insulin like growth factor 2 (Igf2) genes. The H19 ICR is highly methylated in sperm DNA and hypomethylated in oocytes, whereas embryonic stem (ES) cells, carrying a maternal (hypomethylated) and a paternal (methylated) copy, display intermediate methylation (Fig.…”

IGF2: Epigenetic regulation and role in development and disease

“…Almost all known imprinted genes occur in clusters with one or more reciprocally imprinted genes (reviewed in [22]). The mouse Igf2 gene lies on the distal region of chromosome 7 with the oppositely imprinted, non-coding gene H19.…”

Changes in cell cycle and extracellular matrix gene expression during placental development in deer mouse (Peromyscus) hybrids

“…Imprinted genes are those that exhibit expression bias of one parental allele over the other (Tilghman 1999). Imprinted genes are typically found in discrete genomic clusters (Lewis and Reik 2006). The two parental alleles in these regions are distinguished by differential distribution of epigenetic marks such as DNA methylation and histone modifications (Monk et al 1987;Reik et al 1987;Sanford et al 1987;Sapienza et al 1987;Swain et al 1987).…”