Establishment of functional imprinting of the H19 gene in human developing placentae

Abstract

We have found that the imprinted H19 gene can be expressed either biallelically or monoallelically in the developing human placentae. H19 biallelic expression is confined to the placenta until 10 weeks of gestation, after which it becomes exclusively maternal, and does not affect allele-specificity or levels of IGF2 expression. The promoter region of H19 is hypomethylated at all stages of placental development, while the 3' portion shows progressive methylation of the paternal allele with gestation. Our observations demonstrate that the establishment of functional H19 imprinting occurs during the early development of the placenta and provide an opportunity to understand the mechanism by which the H19 primary imprint is manifested in somatic cells.

Monoallelic Expression of HumanPEG1/MESTIs Paralleled by Parent-Specific Methylation in Fetuses

“…Tissue-specific escape or relaxation of im printing was previously observed for the IGF2 gene in adult liver (Kalscheuer et aL} 1993), fetal choroid plexus, and leptomeninges (Ohlsson et al, 1994) and for H19 in placenta. Human H19 is biallelically ex pressed in the placenta at an early stage, which con trasts with consistent monoallelic expression in the mouse placenta (Jinno et al, 1995;Tremblay et a l, 1995).…”

Genomic imprinting and its relevance to genetic diseases

“…The human Wilms tumor gene, WT1, shows an imprinting polymorphism in the placenta, i.e., there are two populations, one with maternal monoallelic expression and the other with biallelic expression (Jinno et al, 1994). The expression of the human HI9 is biallelic in the placenta before 9 weeks of pregnancy, but maternal monoallelic expression is observed after 10 weeks, indicating that the human HI9 imprinting depends upon developmental stages (Jinno et aL, 1995). Because of the difficulty of observations of gene expression in an early human development, it has not yet been confirmed whether other genes are imprinted in man.…”

Epigenetic reprogramming of the human H19 gene in mouse embryonic cells does not erase the primary parental imprint

“…H19 normally exhibits exclusive maternal expression in somatic tissues, in humans as well as in mice (Bartolomei et al 1991;Zhang & Tycko 1992). Biallelic expression of H19, however, has been described in cultured embryos at 6.5 days post-coitum (dpc) (Sasaki et al 1995) and in early developmental stages of human placentas (Jinno et al 1995). Analyses of uniparental mouse embryos also suggest that H19 is biallelically expressed in extraembryonic tissues at 9.5 dpc (Walsh et al 1994), and that the imprinted genes Igf2 and Igf2r are expressed equally from both parental alleles in preimplantation embryos (Latham et al 1994;Gilligan & Solter 1995).…”