To study how external signaling factors and internal regulatory networks affect embryonic stem cell renewal in mice, scientists at Tsinghua University and the Chinese Academy of Sciences in Beijing looked at how SMAD-mediated BMP signaling "balances self-renewal versus differentiation" in Genome Research this week. Mapping gene promoters SMAD1/5 and SMAD4 across the genome, they found that these associate with a group of developmental regulators that are "enriched for H3K27 trimethylation and H3K4 trimethylation bivalent marks and are repressed in the self-renewing state, whereas they are rapidly induced upon differentiation."
In other work, researchers performed an integrative analysis to look for genetic factors affecting liver toxicity linked to acetaminophen. Using an "integrative genetic, transcriptional, and two-dimensional NMR-based metabolomic analysis" on mice, a team led by first authors Hong-Hsing Liu and Peng Lu from Roche found betaine-homocysteine methyltransferase 2 (Bhmt2) as a diet-dependent factor that affected susceptibility to acetaminophen-induced liver toxicity. Bhmt2 exerts its protective effect through S-methylmethionine, which is only produced in plants.
In the November issue, work led by McGill University's Tomi Pastinen examined how genetic variation works in a cell type-specific manner. Combining an expression quantitative trait loci study of primary human osteoblasts with a GWAS for bone mineral density, they took the top 10 loci with SNPs showing strong cis-effects on gene expression in osteoblasts and were able to narrow down two novel BMD loci at SRR and MSH3. "Our results suggest that primary cells relevant to disease phenotypes complement traditional approaches for prioritization and validation of GWAS hits for follow-up studies," says the abstract.
In a methods paper, Australian scientists at Flinders University, Melbourne University, and the Queensland Institute for Medical Research pooled whole blood from patients prior to DNA extraction for a GWAS and were able to see associated variants for eye color, age-related macular degeneration, and pseudoexfoliation syndrome in cohorts not previously studied. "Blood pooling has the potential to reduce GWAS cost by several orders of magnitude and dramatically shorten gene discovery time."