The human and mouse H19 imprinting control regions harbor an evolutionarily conserved silencer element that functions on transgenes in Drosophila.

Differentially methylated regions have been characterized at a number of imprinted gene complexes with important roles in the regulation of monoallelic expression of one or more genes. The differentially methylated imprinting control region (ICR) located upstream of the murine H19 gene has been shown to control the imprinted expression of H19 and the coordinately regulated Igf2 gene by acting as a transcriptional silencer. In this study, we show that the murine ICR maintains this function when tested in an in vivo transgenic Drosophila assay in the absence of DNA methylation.

Epigenetic aspects of differentiation.

A major challenge in biology is to understand how genetic information is interpreted to direct the formation of specialized tissues within a multicellular organism. During differentiation, changes in chromatin structure and nuclear organization establish heritable patterns of gene expression in response to signals. Epigenetic states can be broadly divided into three categories: euchromatin, constitutive heterochromatin and facultative hetereochromatin.

H19 and Igf2--enhancing the confusion?

Genomic imprinting, whereby certain genes are expressed dependent on whether they are maternally or paternally inherited, is restricted to mammals and angiosperm plants. This unusual mode of gene regulation results from the complex interplay between cis-regulatory elements, leading to parent-of-origin-dependent epigenetic modifications and tissue-specific patterns of imprinted gene expression. Many studies of imprinting and imprinted genes have focused on epigenetic effects, such as DNA methylation and chromatin structure.

Histone methylation defines epigenetic asymmetry in the mouse zygote.

The oocyte cytoplasm regulates and enhances the epigenetic asymmetry between parental genomes and, consequently, functional differences observed between them during development in mammals. Here we demonstrate a preferential interaction of HP1beta with the maternal genome immediately after fertilisation in the mouse zygote, which also shows a high level of lysine 9-methylated histone H3. In contrast, the paternal genome has neither HP1beta binding nor methylated histone H3 at these early stages.

Novel conserved elements upstream of the H19 gene are transcribed and act as mesodermal enhancers.

The reciprocally imprinted H19 and Igf2 genes form a co-ordinately regulated 130 kb unit in the mouse controlled by widely dispersed enhancers, epigenetically modified silencers and an imprinting control region (ICR). Comparative human and mouse genomic sequencing between H19 and Igf2 revealed two novel regions of strong homology upstream of the ICR termed H19 upstream conserved regions (HUCs). Mouse HUC1 and HUC2 act as potent enhancers capable of driving expression of an H19 reporter gene in a range of mesodermal tissues.