In a study set to appear online this week in the Proceedings of the National Academy of Sciences, Rockefeller University researchers Fang-Yuan Chang and Sean Brady describe a homology-guided approach for finding new natural products using metagenomic sequence data. The pair demonstrated the feasibility of this method using bulk bacterial DNA from a desert soil sample collected in California, looking in particular for sequences encoding indolotryptoline-based compounds with anti-proliferative activity. The search uncovered a gene cluster that codes for a set of so-called borregomycins, which appear to show promise as anti-proliferative, anticancer, and antibacterial agents. "As traditional natural product discovery methods saturate the chemical space of frequently occurring bacterial secondary metabolites," Chang and Brady note, "homology-guided metagenomic library screening should be useful for the routine discovery of novel natural products that expand on previously under-explored bioactive natural product families."
University of Illinois at Urbana-Champaign genomic biology and informatics researcher Jian Ma led an international team outlining a method for assembling chromosomes from next-generation sequence data with the help of reference information for related species. The researchers demonstrated the feasibility of the method — dubbed "reference-assisted chromosome assembly," or RACA — for predicting the appropriate chromosome fragment assemblies for the Tibetan antelope, using genomic sequence data for 60 of the animals and homology to cattle chromosomes. "Our results indicate that RACA will significantly facilitate the study of chromosome evolution and genome rearrangements for the large number of genomes being sequenced by [next-generation sequencing] that do not have a genetic or physical map," the study's authors say.
Another study online in PNAS this week highlights some of the epigenetic and gene expression shifts involved in circadian rhythms in mammalian tissue, identifying a role for a methyltransferase enzyme called MLL3 in this process. A team from the UK and The Netherlands used a combination of chromatin immunoprecipitation and high-throughput sequencing to track down sequences associated with an activating, circadian-related histone mark called H3K4me3 in mouse liver samples, bringing this data together with information on rhythmically expressed genes in the mouse tissue and more. "Together, our findings strongly support the idea that daily changes in chromatin architecture at the genomic scale take place in mammalian tissue," they report, "and that almost a fifth of circadian gene expression in the liver is associated with variation of a single activating chromatin mark (H3K4me3)."