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The nucleotide 5-methylcytosine is involved in processes crucial in mammalian development, such as X-chromosome inactivation and gene imprinting. In addition, cytosine methylation has long been speculated to be involved in the establishment and maintenance of cell type-specific expression of developmentally regulated genes; however, it has been difficult to identify clear examples of such genes, particularly in humans. Here we provide evidence that cytosine methylation of the maspin gene (SERPINB5) promoter controls, in part, normal cell type-specific SERPINB5 expression. In normal cells expressing SERPINB5, the SERPINB5 promoter is unmethylated and the promoter region has acetylated histones and an accessible chromatin structure. By contrast, normal cells that do not express SERPINB5 have a completely methylated SERPINB5 promoter with hypoacetylated histones, an inaccessible chromatin structure and a transcriptional repression that is relieved by inhibition of DNA methylation. These findings indicate that cytosine methylation is important in the establishment and maintenance of cell type-restricted gene expression. [ABSTRACT FROM AUTHOR]

Epigenetic control participates in processes crucial in mammalian development, such as X-chromosome inactivation, gene imprinting, and cell type-specific gene expression. We provide evidence that the p53-inducible gene 14-3-3σ is a new example of a gene important to human cancer, where epigenetic mechanisms participate in the control of normal cell type-specific expression, as well as aberrant gene silencing in cancer cells. Like a previously identified cell type-specific gene maspin, 14-3-3σ is a p53-inducible gene; however, it participates in G2/M arrest in response to DNA-damaging agents. 14-3-3σ expression is restricted to certain epithelial cell types, including breast and prostate, whereas expression is absent in nonepithelial tissues such as fibroblasts and lymphocytes. In this report, we show that in normal cells expressing 14-3-3σ, the 14.3.3σ CpG island is unmethylated; associated with acetylated histones, unmethylated histone H3 lysine 9; and an accessible chromatin structure. By contrast, normal cells that do not express 14-3-3σ have a methylated 14-3-3σ CpG island with hypoacetylated histones, methylated histone H3 lysine 9, and an inaccessible chromatin structure. These findings extend the spectrum of cell type--specific genes controlled partly by normal epigenetic mechanisms, and suggest that this subset of genes may represent important targets of epigenetic dysregulation in human cancer. [ABSTRACT FROM AUTHOR]

Despite measures to educate the public about the dangers of elemental mercury, spills continue to occur in homes, schools, health care facilities, and other settings, endangering the public's health and requiring costly cleanup. Mercury is most efficiently absorbed by the lungs, and exposure to high levels of mercury vapor after a release can cause cough, sore throat, shortness of breath, nausea, vomiting, diarrhea, headaches, and visual disturbances (1). Children and fetuses are most susceptible to the adverse effects of mercury vapor exposure. Because their organ systems are still developing, children have increased respiratory rates, and they are closer to the ground where mercury vapors are most highly concentrated (2). To summarize key features of recent mercury spills and lessons learned, five state health departments involved in the cleanup (Iowa, Michigan, Missouri, North Carolina, and Wisconsin) compiled data from various sources on nonthermometer mercury spills from 2012 to 2015. The most common sites of contamination were residences, schools and school buses, health care facilities, and commercial and industrial facilities. Children aged <18 years were present in about one third of the spills, with approximately one in seven incidents resulting in symptoms consistent with acute mercury exposure. To protect the public's health after a mercury spill, it is important that local, state, and federal agencies communicate and coordinate effectively to ensure a quick response, and to minimize the spread of contamination. To reduce the number of mercury spills that occur in the United States, public health officials should increase awareness about exchange programs for mercury-containing items and educate school and health care workers about sources of mercury and how to dispose of them properly.

On December 13, 2014, the emergency management system in Lake Delton, Wisconsin, was notified when a male hockey player aged 20 years lost consciousness after participation in an indoor hockey tournament that included approximately 50 hockey players and 100 other attendees. Elevated levels of carbon monoxide (CO) (range = 45 ppm-165 ppm) were detected by the fire department inside the arena. The emergency management system encouraged all players and attendees to seek medical evaluation for possible CO poisoning. The Wisconsin Department of Health Services (WDHS) conducted an epidemiologic investigation to determine what caused the exposure and to recommend preventive strategies. Investigators abstracted medical records from area emergency departments (EDs) for patients who sought care for CO exposure during December 13-14, 2014, conducted a follow-up survey of ED patients approximately 2 months after the event, and conducted informant interviews. Ninety-two persons sought ED evaluation for possible CO exposure, all of whom were tested for CO poisoning. Seventy-four (80%) patients had blood carboxyhemoglobin (COHb) levels consistent with CO poisoning; 32 (43%) CO poisoning cases were among hockey players. On December 15, the CO emissions from the propane-fueled ice resurfacer were demonstrated to be 4.8% of total emissions when actively resurfacing and 2.3% when idling, both above the optimal range of 0.5%-1.0%. Incomplete fuel combustion by the ice resurfacer was the most likely source of elevated CO. CO poisonings in ice arenas can be prevented through regular maintenance of ice resurfacers, installation of CO detectors, and provision of adequate ventilation.

Epigenetic mechanisms involving dynamic changes in posttranslational histone modifications commonly control gene transcription and therefore the execution of all cellular differentiation programs. The differentiation of hematopoietic stem cells into specific progenitor cells and the diverse blood cell types represents a particularly powerful system for the study of epigenetic mechanisms. The hematopoietic system allows one to define mechanisms underlying the establishment and regulation of histone modification patterns covering entire genes and/or chromosomes at distinct stages of differentiation. This chapter reviews progress in elucidating principles underlying epigenetic control of complex loci, specifically focusing on genes differentially expressed during hematopoiesis.