Dynamic Chromatin Organization during Foregut Development Mediated by the Organ Selector Gene PHA-4/FoxA

Central regulators of cell fate, or selector genes, establish the identity of cells by direct regulation of large cohorts of genes. In Caenorhabditis elegans, foregut (or pharynx) identity relies on the FoxA transcription factor PHA-4, which activates different sets of target genes at various times and in diverse cellular environments. An outstanding question is how PHA-4 distinguishes between target genes for appropriate transcriptional control. We have used the Nuclear Spot Assay and GFP reporters to examine PHA-4 interactions with target promoters in living embryos and with single cell resolution. While PHA-4 was found throughout the digestive tract, binding and activation of pharyngeally expressed promoters was restricted to a subset of pharyngeal cells and excluded from the intestine. An RNAi screen of candidate nuclear factors identified emerin (emr-1) as a negative regulator of PHA-4 binding within the pharynx, but emr-1 did not modulate PHA-4 binding in the intestine. Upon promoter association, PHA-4 induced large-scale chromatin de-compaction, which, we hypothesize, may facilitate promoter access and productive transcription. Our results reveal two tiers of PHA-4 regulation. PHA-4 binding is prohibited in intestinal cells, preventing target gene expression in that organ. PHA-4 binding within the pharynx is limited by the nuclear lamina component EMR-1/emerin. The data suggest that association of PHA-4 with its targets is a regulated step that contributes to promoter selectivity during organ formation. We speculate that global re-organization of chromatin architecture upon PHA-4 binding promotes competence of pharyngeal gene transcription and, by extension, foregut development

Mercury in the Canadian Environment: Current Research Challenges

Elevated methyl mercury concentrations are common in fish and other wildlife in ecosystems remote from any industrial point sources. Concern about chronic exposure to methyl mercury for people who depend on fish as a dietary staple has focused attention on mercury sources and cycling processes in rural and remote areas, and on the potential for airborne mercury to travel hundreds to thousands of kilometres. A number of other studies have demonstrated that elevated concentrations of mercury in fish may be attributable to local geological sources. Compared to the large body of literature that is emerging on anthropogenic sources, however, there is a relative lack of research aimed at quantifying the contribution of mercury from natural sources. This has resulted in a debate over the relative significance of anthropogenic and natural mercury inputs to rural and remote lakes. Geoscience research is needed to improve our understanding of the biogeochemical cycling of mercury species released from common sulphide minerals and other crustal sources into soil, sediments, air, water, vegetation and ultimately into the human food chain. Résumé Les niveaux de mercure méthylé sont souvent élevés dans les tissus des poissons et ceux d'autres animaux de la faune des écosystèmes éloignés des sources industrielles. Découlant des préoccupations concernant les risques d'une exposition régulière au mercure méthylé pour les populations dont la diète est basée sur le poisson, les recherches ont porté sur les sources possibles du mercure, ses cycles de transport ainsi que sur la possibilité que le mercure atmosphérique puisse être transporté sur des milliers de kilomètres. D'autres études ont démontré que des sources géologiques pourraient être à l'origine de concentrations élevées en mercure dans les poissons. Si la documentation sur les sources anthropogéniques de mercure est abondante, on constate en contrepartie qu'il n'y a pas assez de recherches scientifiques visant à chiffrer l'apport des sources naturelles. En conséquence, la question de l'apport relatif en mercure des sources anthropogéniques et naturelles en milieu rural et dans les lacs éloignés demeure-t-elle encore matière à discussion. Des études géoscientifiques devront être réalisées afin d'améliorer nos connaissances sur le cycle biochimique des composés du mercure provenant des minéraux de sulfures usuels et d'autres sources crustales, dans le sol, les sédiments, l'air, l'eau, la végétation, et en bout de piste, dans la chaîne alimentaire des humains