In PLoS Genetics this week, an international team of researchers reports that it has identified an over-represented pentamer motif corresponding to the binding site of the homeodomain protein OTX. This protein, they write, plays a pivotal role in the anterior development of all bilaterian species. Using an in vivo reporter gene assay, the team writes it observed that 10 of 23 candidate cis-regulatory elements containing duplicated OTX motifs are active in the anterior neuroectoderm. "These results show that a common cis-regulatory signature corresponding to K50-paired homeodomain transcription factors is found in non-coding sequences flanking anterior neuroectodermal genes in chordate embryos," the team writes. Field-specific selector genes, the researchers say, impose combinations of short tags on their target enhancers, which could account for the evolutionary conservation of regulatory elements controlling field-specific selector genes responsible for the formation of an organism's body plan.
Also in PLoS Genetics, researchers in Japan and Europe examine the role of the actin-related protein Arp6 in gene expression. They mapped Arp6 binding sites along four yeast chromosomes using chromatin immunoprecipitation from wild-type and swr1 deleted cells, and found that a majority of Arp6 binding sites coincide with Swr1 binding sites. "Given that RP genes and telomeres both show association with the nuclear periphery, we monitored the ability of Arp6 to mediate the localization of chromatin to nuclear pores," the researchers write. The team concludes that Arp6 functions both and without the nucleosome remodeler Swr1 to mediate Htz1-dependent and Htz1-independent binding of chromatin domains to nuclear pores. "This association is shown to have modulating effects on gene expression," they say.
In a paper in PLoS One this week, researchers in Texas evaluated the effects of withaferin-A on tumor growth in vitro and in vivo from mice xenograft studies, in order to clarify the role of vimentin, an anti-cancer therapeutic target, in drug-induced responses. "Withaferin-A elicited marked apoptosis and vimentin cleavage in vimentin-expressing tumor cells but significantly less in normal mesenchymal cells," the researchers write, a reponse that was abrogated after vimentin knockdown or by blocking caspase-induced vimentin degradation. The researchers report they saw pronounced anti-angiogenic effects of witherin-A and that it significantly blocked soft tissue sarcoma growth, local recurrence and metastasis in an array of soft tissue sarcoma xenograft experiments.
Also in PLoS One this week, researchers report their study investigating the role of CD14 in induction of lung inflammation in mice by different LPS chemotypes. The team treated wild type and CD14 knock-out mice with different doses of S-LPS and R-LPS and found that at low doses, S-LPS and R-LPS induced neutrophil influx in a CD14-dependent manner. However, the team writes, neutrophil influx and TNF release induced by high doses of S-LPS or R-LPS was diminished in the presence of CD14. The researchers conclude that CD14 modulated effects of both S-LPS and R-LPS within the lung in a similar way and diminish inflammatory response triggered by high doses of either chemotype.