In the Proceedings of the National Academy of Sciences this week, Graham Lord at King's College London has led a study that checked into the genetic factors behind the differentiation of CD4+ T helper cells. In searching for target genes of the transcription factors T-bet and GATA-3, which direct the differentiation of Th cells into Th1 and Th2 cells, they created a genomic map of T-bet and GATA-3 binding in primary human T cells. Most of the target genes they found were previously unknown, with a good proportion being shared by both. According to the abstract, "These data show that the choice between Th1 and Th2 lineage commitment is the result of the opposing action of T-bet and GATA-3 at a shared set of target genes."
Scientists at the University of Calgary have demonstrated that miR-145 directs maturation of the embryonic zebrafish gut. Using transcriptional analysis, they found that the miR-145 is strongly expressed in zebrafish gut smooth muscle, while loss-of-function experiments showed that loss of this miRNA resulted in defects of smooth muscle function, important for digesting food.
Roman Thomas of the Max Planck Institute for Neurological Research at the University of Cologne led work investigating the connection between upstream and downstream dependency along two pathways in cancer, PI3K and MAPK. Here, his team showed that "tumors with genetically activated receptor tyrosine kinases depend on PI3K signaling, whereas tumors with mutations in the RAS/RAF axis depend on MAPK signaling," but also that downstream pathway inhibition was determined by negative feedback loops on the other pathway. Their "systematic chemo-genomics approach," they say, could impact patient stratification in clinical trials.
Finally, at the Centre for Structural and Chemical Biology at the University of Sussex, Yalda Javadi and Ewan Mainat conducted an experiment examining the folding kinetics of repeat proteins containing the tetratricopeptide motif, a 34-aa helix-turn-helix, which is very common. They found that "the energy landscape changes with the addition of repeat units" and that the designed repeat proteins' "highly symmetric, modular native structure is reflected in their multistate kinetics of unfolding and folding," says the abstract.