In a paper recently published online in advance in Cell, a team led by investigators at the Fox Chase Cancer Center in Philadelphia discuss "how unmethylated regions in mammalian genomes are protected from de novo methylation and whether an active demethylating activity is involved," and show that, in mice, "either knockout or catalytic inactivation of the DNA repair enzyme thymine DNA glycosylase leads to embryonic lethality." Overall, team reports that thymine DNA glycosylase, or TDG, "keeps CpG islands unmethylated and actively demethylates promoters and enhancers."
Over in Cell Metabolism, researchers at the Buck Institute for Research on Aging in Novato, Calif., along with their colleagues show that, in C. elegans, "life span extension via eIF4G inhibition is mediated by post-transcriptional remodeling of stress response gene expression." In particular, the Buck Institute-led team shows that inhibition of the C. elegans eIF4G ortholog "IFG-1 … enhances ribosomal loading of stress response mRNAs." In its genome-wide mRNA translation state analysis, the team also found evidence to suggest that "IFG-1 mediates the antagonistic effects on growth and somatic maintenance by regulating ... translation of particular mRNAs based, in part, on transcript length."
In another Cell Metabolism paper published this week, a trio of investigators at Georgia Health Sciences University describes the heat shock transcription factor 1, or HSF1, as a potential target for both the treatment of liver cancer and for the control of hepatic steatosis and insulin resistance, as it "protect cells against environmental stressors." The team says that in hepatocellular carcinoma, "HSF1 activation promotes growth of premalignant cells and HCC development by stimulating lipid biosynthesis and perpetuating chronic hepatic metabolic disease induced by carcinogens." Further, the team presents evidence to suggest that the transcription factor "impairs cancer progression," particularly by "mitigating adverse effects of carcinogens on hepatic metabolism by enhancing insulin sensitivity and sensitizing activation of AMP-activated protein kinase," the authors write.
Researchers at the Max Delbrück Center for Molecular Medicine in Berlin, along with their colleagues, report in Molecular Cell this week their use of PAR-CLIP — an approach based on RNA-protein cross-linking — to detect transcriptome-wide interactions of the human RNA-binding protein HuR. In its paper, the Max Delbrück-led team proposes a "novel role of HuR in splicing by binding to introns," in part because the approximately 26,000 transcriptome-wide HuR binding sites it observed "were, on average, highly conserved, enriched for HuR binding motifs, and mainly located in 3' UTRs."