IGF2 is parentally imprinted during human embryogenesis and in the Beckwith-Wiedemann syndrome.

The phenomenon of parental imprinting involves the preferential expression of one parental allele of a subset of chromosomal genes and has so far only been documented in the mouse. We show here, by exploiting sequence polymorphisms in exon nine of the human insulin-like growth factor 2 (IGF2) gene, that only the paternally-inherited allele is active in embryonic and extra-embryonic cells from first trimester pregnancies. In addition, only the paternal allele is expressed in tissues from a patient who suffered from Beckwith-Wiedemann syndrome. Thus the parental imprinting of IGF2 appears to be evolutionarily conserved from mouse to man and has implications for the generation of the Beckwith-Wiedemann syndrome.

Astronomers meet in phoenix, recount a stellar year.

Despite a tightening of the National Aeronautics and Space Administration's budget and the trouble with the Hubble Space Telescope, astronomers were starry-eyed over their latest findings, presented at the major annual meeting of the American Astronomical Society, (AAS) January 3 to 7. New images and measurements of stars, galaxies, cosmic microwaves, and mysterious gamma rays, along with an exciting nova explosion, made it a bright year for those working with existing orbiting satellites and ground-based telescopes, though uncertain funding clouds the future.

Condensed matter physicists shrink their horizons.

In the world of the condensed matter physicist, a micron is a chasm and a millimeter an ocean. At the March American Physical Society meeting in Seattle, some of the 4500 physicists probed the hazards of the micro world, where weird quantum effects can scramble information. Others outlined its opportunities: Molecular engineering that is leading to new information storage materials, and minute structures that could form tethers and containers in some future nanotechnology.

Researchers defy the physical limits to computation.

Each year's new computing technology, it seems, leaves the last year's in the dust. But physicists are now beginning to tell computer scientists that it can't go on this way. Sooner or later, as computers get smaller, faster, and more complex, the laws of physics will throw up roadblocks to further progress. There's only one way out of this bind: radically new strategies. And some of those strategies are starting to emerge.

Artificial-life researchers try to create social reality.

Some scientists, among them cosmologist Stephen Hawking, argue that computer viruses are alive. A better case might be made for many of the self-replicating silicon-based creatures featured at the fourth Conference on Artificial Life, held on 5 to 8 July in Boston. Researchers from computer science, biology, and other disciplines presented computer programs that, among other things, evolved cooperative strategies in a selfish world and recreated themselves in ever more complex forms.

Physicists rock the standard model in dallas.

The 1400 physicists who converged on Dallas 2 weeks ago for the International High Energy Physics meeting came from all over. Ask them about the state of their field, however, and you'll find a common dream-to go beyond the standard model of particles and forces. For physicists "searching for chinks in the model's armor," as several put it, the elusive, unobtrusive neutrino is a promising object of study. And while the meeting saw the possibility of a superheavy "17-keV" neutrino fade, cosmic ray-produced neutrinos gave new hints of physics in that over-the-rainbow region beyond the standard model.

Successive activation of the platelet-derived growth factor beta receptor and platelet-derived growth factor B genes correlates with the genesis of human choriocarcinoma.

The hydatidiform mole is a benign disease of the placenta characterized by the absence of the maternal genome. Approximately 3% of the reported cases will develop into malignant choriocarcinoma. In situ hybridization analysis reveals that the paternal platelet-derived growth factor (PDGF) beta receptor gene is up to 2 orders of magnitude more active in cytotrophoblasts of the complete hydatidiform moles than in normal placentae. The transition between hyperplasia (complete hydatidiform mole) and neoplasia (choriocarcinoma) in these cells correlates with at least a 10- to 20-fold activation of the PDGF-B gene. Since the neoplastic cytotrophoblasts have maintained an abnormally high level of PDGF beta receptor expression, we propose that a deregulated PDGF autostimulatory loop is involved in the genesis of human choriocarcinoma from hydatidiform moles.

Paternally derived H19 is differentially expressed in malignant and nonmalignant trophoblast.

The paternal allele of the H19 gene has been shown to be transcriptionally inactive in the developing human embryo. Using reverse transcription PCR and RNase protection assays, we demonstrate that expression of H19 is predominantly, but not exclusively, from the maternal allele in the human placenta. In situ hybridization analysis shows strong expression of the H19 gene in eight complete hydatidiform moles, hyperplastic tissues consisting of trophoblasts which contain only paternally derived genetic material, indicating that H19 is not functionally imprinted in this tissue. H19, a putative growth suppressor, is oppositely imprinted to the neighboring insulin-like growth factor II (IGF2) gene and an up-regulation of IGF2 expression has been linked previously to a down-regulation of H19 expression in the progression to Wilms' tumor. Two cases of complete hydatidiform mole which progressed to choriocarcinoma show high levels of expression of both H19 and IGF2. The choriocarcinomas which developed from these complete hydatidiform moles showed similar expression of IGF2 but a decreased number of H19-positive cells, which may reflect selection for cells expressing IGF2 and against those expressing H19 in this tissue.

Developmental-dependent DNA methylation of the IGF2 and H19 promoters is correlated to the promoter activities in human liver development.

We have previously shown that the four promoters of the IGF2 gene are under a tight but dynamic control during human liver development, whereby P3 and P1 are reciprocally active before and after birth respectively while the P2 and P4 promoters are constitutively active at a relatively lower level. In this study, we investigated the methylation status of the promoters P1 and P3 of IGF2 and the promoter region of the H19 gene in developing human livers ranging from fetal to late adult. A region of about 300 bp immediately upstream of the IGF2 exon 5 was found to be subjected to a developmental-specific methylation and this may correlate to the P3 promoter activity. The P1 domain of IGF2 was also found to be methylated in a developmentally-specific pattern. The promoter region of the H19 gene displayed different methylation patterns in different development stages showing decreased general methylation with increase of age. Therefore, regional- and developmental-specific DNA methylation is displayed in the promoter regions of the IGF2 and H19 genes. This may be an important factor involved in gene regulation in the developing human liver.