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Patwardhan et al. describe a high-throughput approach for analyzing at single-nucleotide resolution the DNA regulatory sequences that control gene expression. Characterizing these sequences in a massively parallel manner will be useful for deciphering the regulatory logic of the cell and for synthetic biology.
The safety of induced pluripotent stem cells seems to depend on how they were generated. Miura et al. examine the effects of the c-myc transgene, tissue of origin and selection method on the tumor-forming propensity of iPS-cell derivatives.
Forrester et al. adapt the biotin switch technique for studying reversible protein modification by nitric oxide, by using resin-assisted capture of S-nitrosothiols. This enables more sensitive detection of larger S-nitrosylated proteins and can be coupled with quantitative mass spectrometry to study the kinetics of denitrosylation.
Hosaka et al. show that selection of bacteria for antibiotic resistance can be used to discover new antibacterials. Some of the mutant strains they generated, which bear mutations in RNA polymerase and in a ribosomal protein, produce a previously unknown class of antibacterial called piperidamycin.
Judson et al. show that microRNAs specific to mouse embryonic stem cells can substitute for the reprogramming factor cMyc in the generation of induced pluripotent stem cells. The development of reprogramming methods that do not rely on transgenes may facilitate clinical translation of this technology.
The generation of induced pluripotent stem cells might be improved by replacing the reprogramming transgenes with small molecules. To provide cells suitable for small-molecule screening, Markoulaki et al. segregate the transgenes Oct4, Sox2, Klf4 and c-Myc through breeding, creating mice carrying all possible combinations of the four factors.