VEZF1 elements mediate protection from DNA methylation

There is growing consensus that genome organization and long-range gene regulation involves partitioning of the genome into domains of distinct epigenetic chromatin states. Chromatin insulator or barrier elements are key components of these processes as they can establish boundaries between chromatin states. The ability of elements such as the paradigm β-globin HS4 insulator to block the range of enhancers or the spread of repressive histone modifications is well established. Here we have addressed the hypothesis that a barrier element in vertebrates should be capable of defending a gene from silencing by DNA methylation. Using an established stable reporter gene system, we find that HS4 acts specifically to protect a gene promoter from de novo DNA methylation. Notably, protection from methylation can occur in the absence of histone acetylation or transcription. There is a division of labor at HS4; the sequences that mediate protection from methylation are separable from those that mediate CTCF-dependent enhancer blocking and USF-dependent histone modification recruitment. The zinc finger protein VEZF1 was purified as the factor that specifically interacts with the methylation protection elements. VEZF1 is a candidate CpG island protection factor as the G-rich sequences bound by VEZF1 are frequently found at CpG island promoters. Indeed, we show that VEZF1 elements are sufficient to mediate demethylation and protection of the APRT CpG island promoter from DNA methylation. We propose that many barrier elements in vertebrates will prevent DNA methylation in addition to blocking the propagation of repressive histone modifications, as either process is sufficient to direct the establishment of an epigenetically stable silent chromatin stat

Sleep Apnea and Diabetes: Insights into the Emerging Epidemic

The rampant diabetes pandemic over the last few decades has been associated with an increased rise in cardiovascular events and deaths. Risk factors such as obesity, family history of diabetes, decreased physical activity, and aging are among the most common in the development of diabetes. Emerging evidence in the last 10 years has suggested that sleep apnea is a novel risk factor in the development of diabetes. Associations between diabetes and sleep apnea are supported by both epidemiologic and clinical sleep apnea studies. In this report, we discuss epidemiologic and clinical evidence suggesting that sleep apnea is involved in the pathogenesis of altered glucose metabolism. In light of current evidence, sleep apnea treatment should be incorporated into existing pharmacotherapeutic regimens for optimal management of diabetes among diabetic patients with sleep apnea in order to reduce associated cardiovascular risk. Suggestions to improve practice guidelines in the management of diabetic patients with sleep apnea are provided