Genome-Wide Studies Reveal that H3K4me3 Modification in Bivalent Genes Is Dynamically Regulated during the Pluripotent Cell Cycle and Stabilized upon Differentiation

Indexación: Web of Science; Scopus.Stem cell phenotypes are reflected by posttranslational histone modifications, and this chromatin-related memory must be mitotically inherited to maintain cell identity through proliferative expansion. In human embryonic stem cells (hESCs), bivalent genes with both activating (H3K4me3) and repressive (H3K27me3) histone modifications are essential to sustain pluripotency. Yet, the molecular mechanisms by which this epigenetic landscape is transferred to progeny cells remain to be established. By mapping genomic enrichment of H3K4me3/H3K27me3 in pure populations of hESCs in G2, mitotic, and G1 phases of the cell cycle, we found striking variations in the levels of H3K4me3 through the G2-M-G1 transition. Analysis of a representative set of bivalent genes revealed that chromatin modifiers involved in H3K4 methylation/demethylation are recruited to bivalent gene promoters in a cell cycle-dependent fashion. Interestingly, bivalent genes enriched with H3K4me3 exclusively during mitosis undergo the strongest upregulation after induction of differentiation. Furthermore, the histone modification signature of genes that remain bivalent in differentiated cells resolves into a cell cycle-independent pattern after lineage commitment. These results establish a new dimension of chromatin regulation important in the maintenance of pluripotencyhttp://mcb.asm.org/content/36/4/61

Linkage Study of Schizophrenia with Markers on Chromosome 11 in Two Japanese Pedigrees

We examined the linkage between schizophrenia and DNA markers on chromosome 11 in two Japanese pedigrees. Thirty individuals from the two pedigrees were genotyped at the eleven polymorphisms (eight loci) studied. Data were analyzed according to three models, representing a range of single gene models from near dominant to an intermediate model. For all markers, except those at the D11S35 locus, there is no evidence for the linkage. Positive LOD scores between 1 and 1.5 are obtained for some genetic models with the polymorphism at D11S35. Two point scores for the broad diagnostic model and for the intermediate parameter set peak at 1.49

Comparison of Thiopentone/Guaifenesin, Ketamine/Guaifenesin and Ketamine/Midazolam for the Induction of Horses to Be Anaesthetised with Isoflurane

Forty-eight horses subjected to elective surgery were randomly assigned to three groups of 16 horses. After premedication with 0.1 mg/kg acepromazine intramuscularly and 0.6 mg/kg xylazine intravenously, anaesthesia was induced either with 2 g thiopentone in 500 ml of a 10 per cent guaifenesin solution, given intravenously at a dose of 1 ml/kg (group TG), or with 100 mg/kg guaifenesin and 2.2 mg/kg ketamine given intravenously (group KG), or with 0.06 mg/kg midazolam, and 2.2 mg/kg ketamine given intravenously (group KM). Anaesthesia was maintained with isoflurane. The mean (sd) end tidal isoflurane concentration (per cent) needed to maintain a light surgical anaesthesia (stage III, plane 2) was significantly lower in group KM (0.91 [0.03]) than in groups TG (1.11 [0.03]) and KG (1.14 [0.03]). The mean (sd) arterial pressure (mmHg) was significantly lower in group KG (67.4 [2.07]) than in groups TC (75.6 [2.23]) and KM (81.0 [2.16]). There were no significant differences in the logarithm of the heart rate, recovery time or quality of recovery between the three induction groups. However, pronounced ataxia was observed in the horses of group KM, especially after periods of anaesthesia lasting less than 75 minutes