The H19 and insulin-like growth factor 2 (Igf2) genes in the mouse are models for genomic imprinting during development. The genes are located only 90 kb apart in the same transcriptional orientation [1], but are reciprocally imprinted: Igf2 is paternally expressed while H19 is maternally expressed. It has been suggested that expression of H19 and repression of Igf2 (or the converse) on a given...

Overexpression of insulin growth factor 2 (IGF2) is a hallmark of adrenocortical carcinomas and pheochromocytomas. Previous studies investigating the IGF2/H19 locus have mainly focused on a single molecular level such as genomic alterations or altered DNA methylation levels and the causal changes underlying IGF2 overexpression are still not fully established. In the current study, we analyzed 6...

OBJECTIVE To test the hypothesis that polymorphic variation in the paternally transmitted fetal IGF2 gene is associated with maternal glucose concentrations in the third trimester of pregnancy. RESEARCH DESIGN AND METHODS A total of 17 haplotype tag single nucleotide polymorphisms in the IGF2 gene region were genotyped in 1,160 mother/partner/offspring trios from the prospective Cambridge Bab...

The potent growth-promoting activity of insulin-like growth factor-II (IGF-II) is highly regulated during development but frequently up-regulated in tumors. Increased expression of the normally monoallelic (paternally expressed) mouse (Igf2) and human (IGF2) genes modify progression of intestinal adenoma in the Apc mouse and correlate with a high relative risk of human colorectal cancer suscept...

The distal end of mouse Chromosome 7 contains four tightly linked genes whose expression is dependent on their parental inheritance. Mash-2 and H19 are expressed exclusively from the maternal chromosome, whereas Insulin-2 (Ins-2) and Insulin-like growth factor 2 (Igf2) are paternally expressed. The identical expression during development of the 3'-most genes in the cluster, Igf2 and H19, led to...

The imprinted Igf2 gene is active only on the paternal allele in most tissues. Its imprinting involves a cis-acting imprinting-control region (ICR) located upstream of the neighboring and maternally expressed H19 gene. It is thought that differential methylation of the parental alleles at the ICR is crucial for parental imprinting of both genes. Differentially methylated regions (DMRs) have als...

There is some evidence that insulin-like growth factor 2 (IGF-2) may intervene in the control of T cell differentiation. To further study the immunoregulatory function of this growth factor, we analyzed the immune system of Igf2-/- mice. Phenotypically, some immunological parameters such as lymphoid organ morphology and cellularity were unaltered in Igf2-/- mice, but an increase of CD8+ cells a...

Monoallelic expression of IGF2 is regulated by CCCTC binding factor (CTCF) binding to the imprinting control region (ICR) on the maternal allele, with subsequent formation of an intrachromosomal loop to the promoter region. The N-terminal domain of CTCF interacts with SUZ12, part of the polycomb repressive complex-2 (PRC2), to silence the maternal allele. We synthesized decoy CTCF proteins, fus...

Epigenetic alterations in human cancers include global DNA hypomethylation,gene hypomethylation and promoter hypermethylation, and loss of imprinting (LOI) of the insulin-like growth factor-II gene (IGF2). A mechanism for LOI described previously is hypermethylation of a differentially methylated region (DMR) upstream of the H19 gene, allowing activation of the normally silent maternal allele o...

BACKGROUND To investigate the characteristics of allelic distribution of IGF2 and H19 gene polymorphisms in molar tissues compared to normal placentas. MATERIALS AND METHODS Forty-nine specimens of molar tissues as well as 100 control normal placental tissues, delivered on the same days, were collected. Polymerase chain reaction (PCR) with restriction fragment length polymorphism (RFLP) on 2%...